Throughout their evolutionary history, bacteria have faced diverse threats from other microorganisms, including competing bacteria, bacteriophages and predators. In response to these threats, they have evolved sophisticated defence mechanisms that today also protect bacteria against antibiotics and other therapies. In this Review, we explore the protective strategies of bacteria, including the mechanisms, evolution and clinical implications of these ancient defences. We also review the countermeasures that attackers have evolved to overcome bacterial defences. We argue that understanding how bacteria defend themselves in nature is important for the development of new therapies and for minimizing resistance evolution.
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Xavier, J. C. et al. The metabolic network of the last bacterial common ancestor. Commun. Biol. 4, 413 (2021).
Foster, K. R. & Bell, T. Competition, not cooperation, dominates interactions among culturable microbial species. Curr. Biol. 22, 1845–1850 (2012).
Nadell, C. D., Drescher, K. & Foster, K. R. Spatial structure, cooperation and competition in biofilms. Nat. Rev. Microbiol. 14, 589–600 (2016).
Peterson, S. B., Bertolli, S. K. & Mougous, J. D. The central role of interbacterial antagonism in bacterial life. Curr. Biol. 30, R1203–R1214 (2020).
Palmer, J. D. & Foster, K. R. Bacterial species rarely work together. Science 376, 581–582 (2022).
Chevallereau, A., Pons, B. J., van Houte, S. & Westra, E. R. Interactions between bacterial and phage communities in natural environments. Nat. Rev. Microbiol. 20, 49–62 (2021).
Pérez, J., Moraleda-Muñoz, A., Marcos-Torres, F. J. & Muñoz-Dorado, J. Bacterial predation: 75 years and counting! Environ. Microbiol. 18, 766–779 (2016).
Wein, T. & Sorek, R. Bacterial origins of human cell-autonomous innate immune mechanisms. Nat. Rev. Immunol. 22, 629–638 (2022).
Brockhurst, M. A. et al. Assessing evolutionary risks of resistance for new antimicrobial therapies. Nat. Ecol. Evol. 3, 515–517 (2019).
Granato, E. T., Meiller-Legrand, T. A. & Foster, K. R. The evolution and ecology of bacterial warfare. Curr. Biol. 29, R521–R537 (2019).
Clardy, J., Fischbach, M. A. & Currie, C. R. The natural history of antibiotics. Curr. Biol. 19, R437 (2009).
Hassan, M., Kjos, M., Nes, I. F., Diep, D. B. & Lotfipour, F. Natural antimicrobial peptides from bacteria: characteristics and potential applications to fight against antibiotic resistance. J. Appl. Microbiol. 113, 723–736 (2012).
Riley, M. A. & Wertz, J. E. Bacteriocin diversity: ecological and evolutionary perspectives. Biochimie 84, 357–364 (2002).
Vacheron, J., Heiman, C. M. & Keel, C. Live cell dynamics of production, explosive release and killing activity of phage tail-like weapons for Pseudomonas kin exclusion. Commun. Biol. 4, 87 (2021).
Ho, B. T., Dong, T. G. & Mekalanos, J. J. A view to a kill: the bacterial type VI secretion system. Cell Host Microbe 15, 9–21 (2014).
Nakayama, K. et al. The R-type pyocin of Pseudomonas aeruginosa is related to P2 phage, and the F-type is related to lambda phage. Mol. Microbiol. 38, 213–231 (2000).
Davies, E. V. et al. Temperate phages both mediate and drive adaptive evolution in pathogen biofilms. Proc. Natl Acad. Sci. USA 113, 8266–8271 (2016).
Sharp, C., Bray, J., Housden, N. G., Maiden, M. C. J. & Kleanthous, C. Diversity and distribution of nuclease bacteriocins in bacterial genomes revealed using hidden Markov models. PLoS Comput. Biol. 13, e1005652 (2017).
Cascales, E. et al. Colicin biology. Microbiol. Mol. Biol. Rev. 71, 158–229 (2007).
Chikindas, M. L., Weeks, R., Drider, D., Chistyakov, V. A. & Dicks, L. M. Functions and emerging applications of bacteriocins. Curr. Opin. Biotechnol. 49, 23–28 (2018).
LaCourse, K. D. et al. Conditional toxicity and synergy drive diversity among antibacterial effectors. Nat. Microbiol. 3, 440–446 (2018).
Smith, W. P. J. et al. The evolution of the type VI secretion system as a disintegration weapon. PLoS Biol. 18, e3000720 (2020).
Kohanski, M. A., Dwyer, D. J. & Collins, J. J. How antibiotics kill bacteria: from targets to networks. Nat. Rev. Microbiol. 8, 423–435 (2010).
Boolchandani, M., D’Souza, A. W. & Dantas, G. Sequencing-based methods and resources to study antimicrobial resistance. Nat. Rev. Genet. 20, 356–370 (2019).
Rohwer, F. Global phage diversity. Cell 113, 141 (2003).
Suttle, C. A. The significance of viruses to mortality in aquatic microbial communities. Microb. Ecol. 28, 237–243 (1994).
Secor, P. R. & Dandekar, A. A. More than simple parasites: the sociobiology of bacteriophages and their bacterial hosts. mBio 11, e00041 (2020).
Howard-Varona, C., Hargreaves, K. R., Abedon, S. T. & Sullivan, M. B. Lysogeny in nature: mechanisms, impact and ecology of temperate phages. ISME J. 11, 1511–1520 (2017).
Clokie, M. R. J., Millard, A. D., Letarov, A. V. & Heaphy, S. Phages in nature. Bacteriophage 1, 31–45 (2011).
Fernandes, S. & São-José, C. Enzymes and mechanisms employed by tailed bacteriophages to breach the bacterial cell barriers. Viruses 10, 396 (2018).
Sausset, R., Petit, M. A., Gaboriau-Routhiau, V. & De Paepe, M. New insights into intestinal phages. Mucosal Immunol. 13, 205–215 (2020).
Muñoz-Dorado, J., Marcos-Torres, F. J., García-Bravo, E., Moraleda-Muñoz, A. & Pérez, J. Myxobacteria: moving, killing, feeding, and surviving together. Front. Microbiol. 7, 781 (2016).
Laloux, G. Shedding light on the cell biology of the predatory bacterium Bdellovibrio bacteriovorus. Front. Microbiol. 10, 3136 (2020).
Bratanis, E., Andersson, T., Lood, R. & Bukowska-Faniband, E. Biotechnological potential of Bdellovibrio and like organisms and their secreted enzymes. Front. Microbiol. 11, 662 (2020).
Danczak, R. E. et al. Members of the candidate phyla radiation are functionally differentiated by carbon-and nitrogen-cycling capabilities. Microbiome 5, 112 (2017).
Bor, B. et al. Rapid evolution of decreased host susceptibility drives a stable relationship between ultrasmall parasite TM7x and its bacterial host. Proc. Natl Acad. Sci. USA 115, 12277–12282 (2018).
Blair, J. M. A., Webber, M. A., Baylay, A. J., Ogbolu, D. O. & Piddock, L. J. V. Molecular mechanisms of antibiotic resistance. Nat. Rev. Microbiol. 13, 42–51 (2015).
Wilson, D. N., Hauryliuk, V., Atkinson, G. C. & O’Neill, A. J. Target protection as a key antibiotic resistance mechanism. Nat. Rev. Microbiol. 18, 637–648 (2020).
Larsen, J. et al. Emergence of methicillin resistance predates the clinical use of antibiotics. Nature 602, 135–141 (2022).
Fan, X. Y. et al. Oxidation of dCTP contributes to antibiotic lethality in stationary-phase mycobacteria. Proc. Natl Acad. Sci. USA 115, 2210–2215 (2018).
Dong, T. G. et al. Generation of reactive oxygen species by lethal attacks from competing microbes. Proc. Natl Acad. Sci. USA 112, 2181–2186 (2015).
Wozniak, K. J. & Simmons, L. A. Bacterial DNA excision repair pathways. Nat. Rev. Microbiol. 20, 465–477 (2022).
Kisker, C., Kuper, J. & Van Houten, B. Prokaryotic nucleotide excision repair. Cold Spring Harb. Perspect. Biol. 5, a012591 (2013).
Maviza, T. P. et al. RtcB2-PrfH operon protects E. coli ATCC25922 strain from colicin E3 toxin. Int. J. Mol. Sci. 23, 6453 (2022).
Joly, N. et al. Managing membrane stress: the phage shock protein (Psp) response, from molecular mechanisms to physiology. FEMS Microbiol. Rev. 34, 797–827 (2010).
Hersch, S. J. et al. Envelope stress responses defend against type six secretion system attacks independently of immunity proteins. Nat. Microbiol. 5, 706–714 (2020).
Munita, J. M. & Arias, C. A. Mechanisms of antibiotic resistance. Microbiol. Spectr. https://doi.org/10.1128/microbiolspec.VMBF-0016-2015.
Yang, X., Long, M. & Shen, X. Effector–immunity pairs provide the T6SS nanomachine its offensive and defensive capabilities. Molecules 23, 1009 (2018).
Aoki, S. K. et al. A widespread family of polymorphic contact-dependent toxin delivery systems in bacteria. Nature 468, 439–442 (2010).
Coyne, M. J., Zitomersky, N. L., McGuire, A. M., Earl, A. M. & Comstock, L. E. Evidence of extensive DNA transfer between bacteroidales species within the human gut. MBio 5, e01305-14 (2014).
Ross, B. D. et al. Human gut bacteria contain acquired interbacterial defence systems. Nat 575, 224–228 (2019).
Bush, K. Past and present perspectives on β-lactamases. Antimicrobial. Agents Chemother. 62, e01076-18 (2018).
Tock, M. R. & Dryden, D. T. F. The biology of restriction and anti-restriction. Curr. Opin. Microbiol. 8, 466–472 (2005).
Ofir, G. et al. DISARM is a widespread bacterial defence system with broad anti-phage activities. Nat. Microbiol. 3, 90–98 (2018).
Wang, L., Jiang, S., Deng, Z., Dedon, P. C. & Chen, S. DNA phosphorothioate modification-a new multi-functional epigenetic system in bacteria. FEMS Microbiol. Rev. 43, 109–122 (2019).
Barrangou, R. et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science 315, 1709–1712 (2007).
Westra, E. R. & Levin, B. R. It is unclear how important CRISPR-Cas systems are for protecting natural populations of bacteria against infections by mobile genetic elements. Proc. Natl Acad. Sci. USA 117, 27777–27785 (2020).
Lisitskaya, L., Aravin, A. A. & Kulbachinskiy, A. DNA interference and beyond: structure and functions of prokaryotic Argonaute proteins. Nat. Commun. 9, 5165 (2018).
Gupta, R. S. Origin of diderm (Gram-negative) bacteria: antibiotic selection pressure rather than endosymbiosis likely led to the evolution of bacterial cells with two membranes. Antonie van Leeuwenhoek 100, 171–182 (2011).
Dy, R. L., Richter, C., Salmond, G. P. C. & Fineran, P. C. Remarkable mechanisms in microbes to resist phage infections. Annu. Rev. Virol. 1, 307–331 (2014).
Vidakovic, L., Singh, P. K., Hartmann, R., Nadell, C. D. & Drescher, K. Dynamic biofilm architecture confers individual and collective mechanisms of viral protection. Nat. Microbiol. 3, 26–31 (2017).
Toska, J., Ho, B. T. & Mekalanos, J. J. Exopolysaccharide protects Vibrio cholerae from exogenous attacks by the type 6 secretion system. Proc. Natl Acad. Sci. USA 115, 7997–8002 (2018).
Flaugnatti, N. et al. Human commensal gut Proteobacteria withstand type VI secretion attacks through immunity protein-independent mechanisms. Nat. Commun. 12, 5751 (2021).
Bharat, T. A. M. et al. Structure of the hexagonal surface layer on Caulobacter crescentus cells. Nat. Microbiol. 2, 17059 (2017).
Koval, S. F. & Hynes, S. H. Effect of paracrystalline protein surface layers on predation by Bdellovibrio bacteriovorus. J. Bacteriol. 173, 2244–2249 (1991).
Duncan, M. C. et al. Vibrio cholerae motility exerts drag force to impede attack by the bacterial predator Bdellovibrio bacteriovorus. Nat. Commun. 9, 4757 (2018).
Gao, L. & van der Veen, S. Role of outer membrane vesicles in bacterial physiology and host cell interactions. Infect. Microbes Dis. 2, 3–9 (2020).
Manning, A. J. & Kuehn, M. J. Contribution of bacterial outer membrane vesicles to innate bacterial defense. BMC Microbiol 11, 258 (2011).
Webber, M. A. The importance of efflux pumps in bacterial antibiotic resistance. J. Antimicrob. Chemother. 51, 9–11 (2003).
Saier, M. H. et al. Evolutionary origins of multidrug and drug-specific efflux pumps in bacteria. FASEB J. 12, 265–274 (1998).
Du, D. et al. Multidrug efflux pumps: structure, function and regulation. Nat. Rev. Microbiol. 16, 523–539 (2018).
Tahlan, K. et al. Initiation of actinorhodin export in Streptomyces coelicolor. Mol. Microbiol. 63, 951–961 (2007).
Wadhwa, N. & Berg, H. C. Bacterial motility: machinery and mechanisms. Nat. Rev. Microbiol. 20, 161–173 (2021).
Matz, C. & Jürgens, K. High motility reduces grazing mortality of planktonic bacteria. Appl. Environ. Microbiol. 71, 921–929 (2005).
Lambert, C. et al. Characterizing the flagellar filament and the role of motility in bacterial prey-penetration by Bdellovibrio bacteriovorus. Mol. Microbiol. 60, 274–286 (2006).
Bertozzi Silva, J., Storms, Z. & Sauvageau, D. Host receptors for bacteriophage adsorption. FEMS Microbiol. Lett. 363, 2 (2016).
Li, X., Gonzalez, F., Esteves, N., Scharf, B. E. & Chen, J. Formation of phage lysis patterns and implications on co-propagation of phages and motile host bacteria. PLoS Comput. Biol. 16, e1007236 (2020).
Granato, E. T., Smith, W. P. J. & Foster, K. R. Collective protection against the type VI secretion system in bacteria. Preprint at bioRxiv https://doi.org/10.1101/2022.09.12.507624 (2022).
Cornforth, D. M. & Foster, K. R. Competition sensing: the social side of bacterial stress responses. Nat. Rev. Microbiol. 11, 285–293 (2013).
Oliveira, N. M. et al. Biofilm formation as a response to ecological competition. PLoS Biol. 13, e1002191 (2015).
Lories, B. et al. Biofilm bacteria use stress responses to detect and respond to competitors. Curr. Biol. 30, 1231–1244.e4 (2020).
Sadiq, F. A. et al. Phenotypic and genetic heterogeneity within biofilms with particular emphasis on persistence and antimicrobial tolerance. Future Microbiol. 12, 1087–1107 (2017).
Krishna Kumar, R. et al. Droplet printing reveals the importance of micron-scale structure for bacterial ecology. Nat. Commun. 12, 857 (2021).
Bagge, N. et al. Dynamics and spatial distribution of β-lactamase expression in Pseudomonas aeruginosa biofilms. Antimicrob. Agents Chemother. 48, 1168–1174 (2004).
Billings, N. et al. The extracellular matrix component psl provides fast-acting antibiotic defense in Pseudomonas aeruginosa biofilms. PLoS Pathog. 9, e1003526 (2013).
Wucher, B. R., Elsayed, M., Adelman, J. S., Kadouri, D. E. & Nadell, C. D. Bacterial predation transforms the landscape and community assembly of biofilms. Curr. Biol. 31, 2643–2651 (2021).
Xavier, J. B. & Foster, K. R. Cooperation and conflict in microbial biofilms. Proc. Natl Acad. Sci. USA 104, 876–881 (2007).
Bond, M. C., Vidakovic, L., Singh, P. K., Drescher, K. & Nadell, C. D. Matrix-trapped viruses can prevent invasion of bacterial biofilms by colonizing cells. eLife 10, e65355 (2021).
Arnoldini, M. et al. Bistable expression of virulence genes in Salmonella leads to the formation of an antibiotic-tolerant subpopulation. PLoS Biol. 12, e1001928 (2014).
Łapińska, U. et al. Fast bacterial growth reduces antibiotic accumulation and efficacy. eLife 11, e74062 (2022).
Williamson, K. S. et al. Heterogeneity in Pseudomonas aeruginosa biofilms includes expression of ribosome hibernation factors in the antibiotic-tolerant subpopulation and hypoxia-induced stress response in the metabolically active population. J. Bacteriol. 194, 2062–2073 (2012).
Balaban, N. Q., Merrin, J., Chait, R., Kowalik, L. & Leibler, S. Bacterial persistence as a phenotypic switch. Science 305, 1622–1625 (2004).
Van Den Bergh, B. et al. Frequency of antibiotic application drives rapid evolutionary adaptation of Escherichia coli persistence. Nat. Microbiol. 1, 16020 (2016).
Drebes Dörr, N. C. & Blokesch, M. Interbacterial competition and anti‐predatory behaviour of environmental Vibrio cholerae strains. Environ. Microbiol. 22, 4485–4504 (2020).
Basler, M., Ho, B. T. & Mekalanos, J. J. Tit-for-Tat: type VI secretion system counterattack during bacterial cell-cell interactions. Cell 152, 884–894 (2013).
Kamal, F. et al. Differential cellular response to translocated toxic effectors and physical penetration by the type VI secretion system. Cell Rep. 31, 107766 (2020).
Rendueles, O., Amherd, M. & Velicer, G. J. Positively frequency-dependent interference competition maintains diversity and pervades a natural population of cooperative microbes. Curr. Biol. 25, 1673–1681 (2015).
Gordon, D. M. & Riley, M. A. A theoretical and empirical investigation of the invasion dynamics of colicinogeny. Microbiology 145, 655–661 (1999).
Booth, S. C., Smith, W. P. J. & Foster, K. R. Bows and swords: why bacteria carry short and long-range weapons. Preprint at bioRxiv https://doi.org/10.1101/2022.10.13.512033 (2022).
Mavridou, D. A. I., Gonzalez, D., Kim, W., West, S. A. & Correspondence, K. R. F. Bacteria use collective behavior to generate diverse combat strategies. Curr. Biol. 28, 345–355.e4 (2018).
Gonzalez, D., Sabnis, A., Foster, K. R. & Mavridou, D. A. I. Costs and benefits of provocation in bacterial warfare. Proc. Natl Acad. Sci. USA 115, 7593–7598 (2018).
Lopatina, A., Tal, N. & Sorek, R. Abortive infection: bacterial suicide as an antiviral immune strategy. Annu. Rev. Virol. 7, 371–384 (2020).
Johnson, A. G. et al. Bacterial gasdermins reveal an ancient mechanism of cell death. Science 375, 221–225 (2022).
Cohen, D. et al. Cyclic GMP–AMP signalling protects bacteria against viral infection. Nature 574, 691–695 (2019).
Koga, M., Otsuka, Y., Lemire, S. & Yonesaki, T. Escherichia coli rnlA and rnlB compose a novel toxin–antitoxin system. Genetics 187, 123–130 (2011).
Watson, B. N. J. et al. Type I-F CRISPR-Cas resistance against virulent phages results in abortive infection and provides population-level immunity. Nat. Commun. 10, 5526 (2019).
Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077 (2020).
Ka, D., Oh, H., Park, E., Kim, J. H. & Bae, E. Structural and functional evidence of bacterial antiphage protection by Thoeris defense system via NAD+ degradation. Nat. Commun. 11, 2816 (2020).
Doron, S. et al. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 359, eaar4120 (2018).
Geller, A. M. et al. The extracellular contractile injection system is enriched in environmental microbes and associates with numerous toxins. Nat. Commun. 12, 3743 (2021).
Granato, E. T. & Foster, K. R. The evolution of mass cell suicide in bacterial warfare. Curr. Biol. 30, 2836–2843.e3 (2020).
Niehus, R., Oliveira, N. M., Li, A., Fletcher, A. G. & Foster, K. R. The evolution of strategy in bacterial warfare via the regulation of bacteriocins and antibiotics. eLife https://doi.org/10.7554/eLife.69756.
Boor, K. J. Bacterial stress responses: what doesn’t kill them can make them stronger. PLoS Biol. 4, 0018–0020 (2006).
Shin, J. H., Singh, A. K., Cheon, D. J. & Roe, J. H. Activation of the SoxR regulon in Streptomyces coelicolor by the extracellular form of the pigmented antibiotic actinorhodin. J. Bacteriol. 193, 75–81 (2011).
Smith, W. P. J. et al. The evolution of tit-for-tat in bacteria via the type VI secretion system. Nat. Commun. 11, 5395 (2020).
Wang, G. Z. et al. Staphylococcal secreted cytotoxins are competition sensing signals for Pseudomonas aeruginosa. Preprint at bioRxiv https://doi.org/10.1101/2023.01.29.526047 (2023).
Flores-Kim, J. & Darwin, A. J. The phage shock protein response. Annu. Rev. Microbiol. 70, 83–101 (2016).
Fallico, V., Ross, R. P., Fitzgerald, G. F. & McAuliffe, O. Genetic response to bacteriophage infection in Lactococcus lactis reveals a four-strand approach involving induction of membrane stress proteins, d-alanylation of the cell wall, maintenance of proton motive force, and energy conservation. J. Virol. 85, 12032–12042 (2011).
Song, S. & Wood, T. K. A primary physiological role of toxin/antitoxin systems is phage inhibition. Front. Microbiol. 11, 1895 (2020).
Aijaz, I. & Koudelka, G. B. Cheating, facilitation and cooperation regulate the effectiveness of phage-encoded exotoxins as antipredator molecules. Microbiologyopen 8, e00636 (2019).
Pacheco, A. R. & Sperandio, V. Shiga toxin in enterohemorrhagic E. coli: regulation and novel anti-virulence strategies. Front. Cell. Infect. Microbiol. 2, 81 (2012).
Lambert, C., Ivanov, P. & Sockett, R. E. A transcriptional ‘scream’ early response of E. coli prey to predatory invasion by Bdellovibrio. Curr. Microbiol. 60, 419–427 (2010).
LeRoux, M., Peterson, S. B. & Mougous, J. D. Bacterial danger sensing. J. Mol. Biol. 427, 3744–3753 (2015).
Bertsche, U., Mayer, C., Götz, F. & Gust, A. A. Peptidoglycan perception — sensing bacteria by their common envelope structure. Int. J. Med. Microbiol. 305, 217–223 (2015).
Diggle, S. P., Gardner, A., West, S. A. & Griffin, A. S. Evolutionary theory of bacterial quorum sensing: when is a signal not a signal? Philos. Trans. R. Soc. B Biol. Sci. 362, 1241–1249 (2007).
Pohnert, G., Steinke, M. & Tollrian, R. Chemical cues, defence metabolites and the shaping of pelagic interspecific interactions. Trends Ecol. Evol. 22, 198–204 (2007).
Mazzola, M., De Bruijn, I., Cohen, M. F. & Raaijmakers, J. M. Protozoan-induced regulation of cyclic lipopeptide biosynthesis is an effective predation defense mechanism for Pseudomonas fluorescens. Appl. Environ. Microbiol. 75, 6804–6811 (2009).
Li, L. et al. Sensor histidine kinase is a β-lactam receptor and induces resistance to β-lactam antibiotics. Proc. Natl Acad. Sci. USA 113, 1648–1653 (2016).
Bru, J. L. et al. PQS produced by the Pseudomonas aeruginosa stress response repels swarms away from bacteriophage and antibiotics. J. Bacteriol. 201, e00383-19 (2019).
Tzipilevich, E., Pollak‐Fiyaksel, O., Shraiteh, B. & Ben‐Yehuda, S. Bacteria elicit a phage tolerance response subsequent to infection of their neighbors. EMBO J. 41, e109247 (2022).
LeRoux, M. et al. Kin cell lysis is a danger signal that activates antibacterial pathways of Pseudomonas aeruginosa. eLife 2015, e05701 (2015).
Ting, S. Y. et al. Discovery of coordinately regulated pathways that provide innate protection against interbacterial antagonism. eLife 11, e74658 (2022).
Irving, S. E., Choudhury, N. R. & Corrigan, R. M. The stringent response and physiological roles of (pp)pGpp in bacteria. Nat. Rev. Microbiol. 19, 256–271 (2020).
Inaoka, T., Takahashi, K., Ohnishi-Kameyama, M., Yoshida, M. & Ochi, K. Guanine nucleotides guanosine 5′-diphosphate 3′-diphosphate and GTP co-operatively regulate the production of an antibiotic bacilysin in Bacillus subtilis. J. Biol. Chem. 278, 2169–2176 (2003).
Kuhar, I. & Žgur-Bertok, D. Transcription regulation of the colicin K cka gene reveals induction of colicin synthesis by differential responses to environmental signals. J. Bacteriol. 181, 7373–7380 (1999).
Ochi, K. Occurrence of the stringent response in Streptomyces sp. and its significance for the initiation of morphological and physiological differentiation. J. Gen. Microbiol. 132, 2621–2631 (1986).
Hammer, B. K. & Bassler, B. L. Quorum sensing controls biofilm formation in Vibrio cholerae. Mol. Microbiol. 50, 101–104 (2003).
Rutherford, S. T. & Bassler, B. L. Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb. Perspect. Med. 2, a012427 (2012).
Høyland-Kroghsbo, N. M. et al. Quorum sensing controls the Pseudomonas aeruginosa CRISPR-Cas adaptive immune system. Proc. Natl Acad. Sci. USA 114, 131–135 (2017).
Zhou, L., Zhang, Y., Ge, Y., Zhu, X. & Pan, J. Regulatory mechanisms and promising applications of quorum sensing-inhibiting agents in control of bacterial biofilm formation. Front. Microbiol. 11, 2558 (2020).
Palmer, J. D. & Foster, K. R. The evolution of spectrum in antibiotics and bacteriocins. Proc. Natl Acad. Sci. USA 119, e2205407119 (2022).
Fontaine, L. et al. Quorum-sensing regulation of the production of Blp bacteriocins in Streptococcus thermophilus. J. Bacteriol. 189, 7195 (2007).
Silverman, J. M., Brunet, Y. R., Cascales, E. & Mougous, J. D. Structure and regulation of the type VI secretion system. Annu. Rev. Microbiol. 66, 453 (2012).
Meirelles, L. A., Perry, E. K., Bergkessel, M. & Newman, D. K. Bacterial defenses against a natural antibiotic promote collateral resilience to clinical antibiotics. PLoS Biol. 19, e3001093 (2021).
Darwin, C. On the Origin of Species: A Facsimile of the First Edition (Harvard University Press, 2003).
Raeside, C. et al. Large chromosomal rearrangements during a long-term evolution experiment with Escherichia coli. MBio 5, 1377–1391 (2014).
Frazão, N., Sousa, A., Lässig, M. & Gordo, I. Horizontal gene transfer overrides mutation in Escherichia coli colonizing the mammalian gut. Proc. Natl Acad. Sci. USA 116, 17906–17915 (2019).
Woodford, N. & Ellington, M. J. The emergence of antibiotic resistance by mutation. Clin. Microbiol. Infect. 13, 5–18 (2007).
Macwana, S. & Muriana, P. M. Spontaneous bacteriocin resistance in Listeria monocytogenes as a susceptibility screen for identifying different mechanisms of resistance and modes of action by bacteriocins of lactic acid bacteria. J. Microbiol. Methods 88, 7–13 (2012).
Riley, M. A. & Gordon, D. M. The ecology and evolution of bacteriocins. J. Ind. Microbiol. Biotechnol. 17, 151–158 (1996).
Wright, R. C. T., Friman, V.-P., Smith, M. C. M. & Brockhurst, M. A. Cross-resistance is modular in bacteria–phage interactions. PLoS Biol. 16, e2006057 (2018).
Abouzeed, Y. M., Baucheron, S. & Cloeckaert, A. ramR mutations involved in efflux-mediated multidrug resistance in Salmonella enterica serovar Typhimurium. Antimicrob. Agents Chemother. 52, 2428–2434 (2008).
Cannatelli, A. et al. MgrB inactivation is a common mechanism of colistin resistance in KPC-producing klebsiella pneumoniae of clinical origin. Antimicrob. Agents Chemother. 58, 5696–5703 (2014).
Koch, G. et al. Evolution of resistance to a last-resort antibiotic in Staphylococcus aureus via bacterial competition. Cell 158, 1060–1071 (2014).
Bjedov, I. et al. Stress-induced mutagenesis in bacteria. Sci 300, 1404–1409 (2003).
Krašovec, R. et al. Opposing effects of final population density and stress on Escherichia coli mutation rate. ISME J. 12, 2981–2987 (2018).
Ram, Y. & Hadany, L. Evolution of stress-induced mutagenesis in the presence of horizontal gene transfer. Am. Nat. 194, 73–89 (2019).
MacLean, R. C. & San Millan, A. The evolution of antibiotic resistance. Science 365, 1082–1083 (2019).
Hall, J. P. J., Brockhurst, M. A. & Harrison, E. Sampling the mobile gene pool: innovation via horizontal gene transfer in bacteria. Philos. Trans. R. Soc. B Biol. Sci. 372, 20160424 (2017).
Meaden, S. & Fineran, P. C. Bacterial defense islands limit viral attack. Science 374, 399–400 (2021).
Didelot, X. & Maiden, M. C. J. Impact of recombination on bacterial evolution. Trends Microbiol. 18, 315 (2010).
San Millan, A. Evolution of plasmid-mediated antibiotic resistance in the clinical context. Trends Microbiol. 26, 978–985 (2018).
Botelho, J. & Schulenburg, H. The role of integrative and conjugative elements in antibiotic resistance evolution. Trends Microbiol. 29, 8–18 (2021).
Ruhe, Z. C. et al. CDI systems are stably maintained by a cell-contact mediated surveillance mechanism. PLoS Genet. 12, e1006145 (2016).
Makarova, K. S., Wolf, Y. I., Snir, S. & Koonin, E. V. Defense islands in bacterial and archaeal genomes and prediction of novel defense systems. J. Bacteriol. 193, 6039–6056 (2011).
Bernheim, A. & Sorek, R. The pan-immune system of bacteria: antiviral defence as a community resource. Nat. Rev. Microbiol. 18, 113–119 (2019).
Rocha, E. P. C. & Bikard, D. Microbial defenses against mobile genetic elements and viruses: Who defends whom from what? PLoS Biol. 20, e3001514 (2022).
Costa, R., Van Aarle, I. M., Mendes, R. & Van Elsas, J. D. Genomics of pyrrolnitrin biosynthetic loci: evidence for conservation and whole-operon mobility within Gram-negative bacteria. Environ. Microbiol. 11, 159–175 (2009).
Jousset, A., Rochat, L., Scheu, S., Bonkowski, M. & Keel, C. Predator-prey chemical warfare determines the expression of biocontrol genes by rhizosphere-associated Pseudomonas fluorescens. Appl. Environ. Microbiol. 76, 5263–5268 (2010).
Alexander, H. K. & MacLean, Craig R. Stochastic bacterial population dynamics restrict the establishment of antibiotic resistance from single cells. Proc. Natl Acad. Sci. USA 117, 19455–19464 (2020).
Herron, M. D. et al. De novo origins of multicellularity in response to predation. Sci. Rep. 9, 2328 (2019).
Koskella, B. & Brockhurst, M. A. Bacteria–phage coevolution as a driver of ecological and evolutionary processes in microbial communities. FEMS Microbiol. Rev. 38, 916 (2014).
Libberton, B., Horsburgh, M. J. & Brockhurst, M. A. The effects of spatial structure, frequency dependence and resistance evolution on the dynamics of toxin-mediated microbial invasions. Evol. Appl. 8, 738–750 (2015).
Butela, K. & Lawrence, J. in Bacterial Population Genetics in Infectious Disease (eds Robinson, D. A., Falush, D. & Feil, E. J.) 287–319 (John Wiley & Sons, Ltd, 2010).
Wildschutte, H., Wolfe, D. M., Tamewitz, A. & Lawrence, J. G. Protozoan predation, diversifying selection, and the evolution of antigenic diversity in Salmonella. Proc. Natl Acad. Sci. USA 101, 10644–10649 (2004).
Mostowy, R. J. & Holt, K. E. Diversity-generating machines: genetics of bacterial sugar-coating. Trends Microbiol. 26, 1008–1021 (2018).
Burmeister, A. R. et al. Pleiotropy complicates a trade-off between phage resistance and antibiotic resistance. Proc. Natl Acad. Sci. USA 117, 11207–11216 (2020).
German, G. J. & Misra, R. The TolC protein of Escherichia coli serves as a cell-surface receptor for the newly characterized TLS bacteriophage. J. Mol. Biol. 308, 579–585 (2001).
Andersson, D. I. & Hughes, D. Antibiotic resistance and its cost: Is it possible to reverse resistance? Nat. Rev. Microbiol. 8, 260–271 (2010).
Puigbò, P., Makarova, K. S., Kristensen, D. M., Wolf, Y. I. & Koonin, E. V. Reconstruction of the evolution of microbial defense systems. BMC Evol. Biol. 17, 94 (2017).
Rowe-Magnus, D. A. & Mazel, D. The role of integrons in antibiotic resistance gene capture. Int. J. Med. Microbiol. 292, 115–125 (2002).
Akrami, F., Rajabnia, M. & Pournajaf, A. Resistance integrons; a mini review. Casp. J. Intern. Med. 10, 370–376 (2019).
Hocquet, D. et al. Evidence for induction of integron-based antibiotic resistance by the SOS response in a clinical setting. PLoS Pathog. 8, 1002778 (2012).
Souque, C., Escudero, J. A. & Maclean, R. C. Integron activity accelerates the evolution of antibiotic resistance. eLife 10, e62474 (2021).
Oliveira, P. H., Touchon, M. & Rocha, E. P. C. The interplay of restriction-modification systems with mobile genetic elements and their prokaryotic hosts. Nucleic Acids Res. 42, 10618–10631 (2014).
Alcalde-Rico, M., Hernando-Amado, S., Blanco, P. & Martínez, J. Multidrug efflux pumps at the crossroad between antibiotic resistance and bacterial virulence. Front. Microbiol. 7, 1483 (2016).
van Houte, S., Buckling, A. & Westra, E. R. Evolutionary ecology of prokaryotic immune mechanisms. Microbiol. Mol. Biol. Rev. 80, 745–763 (2016).
Avrani, S., Wurtzel, O., Sharon, I., Sorek, R. & Lindell, D. Genomic island variability facilitates Prochlorococcus–virus coexistence. Nature 474, 604–608 (2011).
Cordero, O. X. et al. Ecological populations of bacteria act as socially cohesive units of antibiotic production and resistance. Science 337, 1228–1231 (2012).
Hussain, F. A. et al. Rapid evolutionary turnover of mobile genetic elements drives bacterial resistance to phages. Science 374, 488–492 (2021).
Hunter, M. & Fusco, D. Superinfection exclusion: a viral strategy with short-term benefits and long-term drawbacks. PLoS Comput. Biol. 18, e1010125 (2022).
Van Melderen, L. & De Bast, M. S. Bacterial toxin–antitoxin systems: more than selfish entities? PLoS Genet. 5, e1000437 (2009).
Koonin, E. V. & Makarova, K. S. Origins and evolution of CRISPR-Cas systems. Philos. Trans. R. Soc. B 374, 20180087 (2019).
Dawkins, R. & Krebs, J. R. Arms races between and within species. Proc. R. Soc. Lond. Ser. B. Biol. Sci. 205, 489–511 (1979).
Kerr, B., Riley, M. A., Feldman, M. W. & Bohannan, B. J. M. Local dispersal promotes biodiversity in a real-life game of rock–paper–scissors. Nature 418, 171–174 (2002).
Longdon, B., Brockhurst, M. A., Russell, C. A., Welch, J. J. & Jiggins, F. M. The evolution and genetics of virus host shifts. PLoS Pathog. 10, e1004395 (2014).
Friman, V.-P. & Buckling, A. Effects of predation on real-time host-parasite coevolutionary dynamics. Ecol. Lett. 16, 39–46 (2013).
Paterson, S. et al. Antagonistic coevolution accelerates molecular evolution. Nature 464, 275–278 (2010).
Czárán, T. L., Hoekstra, R. F. & Pagie, L. Chemical warfare between microbes promotes biodiversity. Proc. Natl Acad. Sci. USA 99, 786 (2002).
Riley, M. A. Positive selection for colicin diversity in bacteria. Mol. Biol. Evol. 10, 1048–1059 (1993).
Gordon, D. M. & O’Brien, C. L. Bacteriocin diversity and the frequency of multiple bacteriocin production in Escherichia coli. Microbiology 152, 3239–3244 (2006).
Michel-Briand, Y. & Baysse, C. The pyocins of Pseudomonas aeruginosa. Biochimie 84, 499–510 (2002).
Merker, M. et al. Evolutionary approaches to combat antibiotic resistance: opportunities and challenges for precision medicine. Front. Immunol. 11, 1938 (2020).
Paradkar, A. Clavulanic acid production by Streptomyces clavuligerus: biogenesis, regulation and strain improvement. J. Antibiot. 66, 411–420 (2013).
Lee, M. D. et al. Microbial fermentation-derived inhibitors of efflux-pump-mediated drug resistance. Farmaco 56, 81–85 (2001).
Bambeke, F., Pages, J.-M. & Lee, V. Inhibitors of bacterial efflux pumps as adjuvants in antibiotic treatments and diagnostic tools for detection of resistance by efflux. Recent. Pat. Antiinfect. Drug Discov. 1, 157–175 (2008).
Braun, V., Pramanik, A., Gwinner, T., Köberle, M. & Bohn, E. Sideromycins: tools and antibiotics. BioMetals 22, 3–13 (2009).
Tillotson, G. Trojan horse antibiotics — a novel way to circumvent Gram-negative bacterial resistance? Infect. Dis. 9, 45–52 (2016).
Coulthurst, S. The type VI secretion system: a versatile bacterial weapon. Microbiol 165, 503–515 (2019).
Boles, B. R. & Horswill, A. R. agr-Mediated dispersal of Staphylococcus aureus biofilms. PLoS Pathog. 4, e1000052 (2008).
Paluch, E., Rewak-Soroczyńska, J., Jędrusik, I., Mazurkiewicz, E. & Jermakow, K. Prevention of biofilm formation by quorum quenching. Appl. Microbiol. Biotechnol. 104, 1871–1881 (2020).
Samson, J. E., Magadán, A. H., Sabri, M. & Moineau, S. Revenge of the phages: defeating bacterial defences. Nat. Rev. Microbiol. 11, 675–687 (2013).
Auer, B. & Schweiger, M. Evidence that Escherichia coli virus T1 induces a DNA methyltransferase. J. Virol. 49, 588–590 (1984).
Iida, S., Streiff, M. B., Bickle, T. A. & Arber, W. Two DNA antirestriction systems of bacteriophage P1, darA, and darB: characterization of darA− phages. Virology 157, 156–166 (1987).
Pawluk, A., Davidson, A. R. & Maxwell, K. L. Anti-CRISPR: discovery, mechanism and function. Nat. Rev. Microbiol. 16, 12–17 (2018).
Scholl, D., Adhya, S. & Merril, C. Escherichia coli K1’s capsule is a barrier to bacteriophage T7. Appl. Environ. Microbiol. 71, 4872–4874 (2005).
Otsuka, Y. & Yonesaki, T. Dmd of bacteriophage T4 functions as an antitoxin against Escherichia coli LsoA and RnlA toxins. Mol. Microbiol. 83, 669–681 (2012).
Erez, Z. et al. Communication between viruses guides lysis–lysogeny decisions. Nature 541, 488–493 (2017).
Jousset, A. Ecological and evolutive implications of bacterial defences against predators. Environ. Microbiol. 14, 1830–1843 (2012).
Kaplan, F. et al. Bacterial attraction and quorum sensing inhibition in Caenorhabditis elegans exudates. J. Chem. Ecol. 35, 878–892 (2009).
Adli, M. The CRISPR tool kit for genome editing and beyond. Nat. Commun. 9, 1911 (2018).
Bernheim, A. et al. Prokaryotic viperins produce diverse antiviral molecules. Nature 589, 120–124 (2021).
Raffatellu, M. Learning from bacterial competition in the host to develop antimicrobials. Nat. Med. 24, 1097–1103 (2018).
Ghosh, C., Sarkar, P., Issa, R. & Haldar, J. Alternatives to conventional antibiotics in the era of antimicrobial resistance. Trends Microbiol. 27, 323–338 (2019).
Hiltunen, T., Virta, M. & Anna-Liisa, L. Antibiotic resistance in the wild: an eco-evolutionary perspective. Philos. Trans. R. Soc. B Biol. Sci. 372, 20160039 (2017).
Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat. Microbiol. 7, 1568–1579 (2022).
Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556–1569.e5 (2022).
Coyte, K. Z., Schluter, J. & Foster, K. R. The ecology of the microbiome: networks, competition, and stability. Science 350, 663–666 (2015).
Coyte, K. Z., Rao, C., Rakoff-Nahoum, S. & Foster, K. R. Ecological rules for the assembly of microbiome communities. PLoS Biol. 19, e3001116 (2021).
García-Bayona, L. & Comstock, L. E. Bacterial antagonism in host-associated microbial communities. Science 361, eaat2456 (2018).
Ventola, C. The antibiotic resistance crisis: part 1: causes and threats. PT 40, 277–283 (2015).
Aminov, R. I. & Mackie, R. I. Evolution and ecology of antibiotic resistance genes. FEMS Microbiol. Lett. 271, 147–161 (2007).
Abrudan, M. I. et al. Socially mediated induction and suppression of antibiosis during bacterial coexistence. Proc. Natl Acad. Sci. USA 112, 11054–11059 (2015).
González-Bello, C. Antibiotic adjuvants — a strategy to unlock bacterial resistance to antibiotics. Bioorg. Med. Chem. Lett. 27, 4221–4228 (2017).
Zhang, Z. et al. Antibiotic production in Streptomyces is organized by a division of labor through terminal genomic differentiation. Sci. Adv. 6, eaay5781 (2020).
Batra, A. et al. High potency of sequential therapy with only β-lactam antibiotics. eLife 10, e68876 (2021).
Beardmore, R. E., Peña-Miller, R., Gori, F., Iredell, J. & Barlow, M. Antibiotic cycling and antibiotic mixing: which one best mitigates antibiotic resistance? Mol. Biol. Evol. 34, 802–817 (2017).
Baym, M., Stone, L. K. & Kishony, R. Multidrug evolutionary strategies to reverse antibiotic resistance. Science 351, aad3292 (2016).
Jamet, A. et al. A widespread family of polymorphic toxins encoded by temperate phages. BMC Biol. 15, 1–12 (2017).
Wang, M. et al. Modular design of membrane-active antibiotics: from macromolecular antimicrobials to small scorpionlike peptidomimetics. J. Med. Chem. 64, 9894–9905 (2021).
Trejo-Hernández, A., Andrade-Domínguez, A., Hernández, M. & Encarnación, S. Interspecies competition triggers virulence and mutability in Candida albicans–Pseudomonas aeruginosa mixed biofilms. ISME J. 8, 1974–1988 (2014).
Flint, A., Stintzi, A. & Saraiva, L. M. Oxidative and nitrosative stress defences of Helicobacter and Campylobacter species that counteract mammalian immunity. FEMS Microbiol. Rev. 40, 938–960 (2016).
Wille, J. & Coenye, T. Biofilm dispersion: the key to biofilm eradication or opening Pandora’s box? Biofilm 2, 100027 (2020).
Dieltjens, L. et al. Inhibiting bacterial cooperation is an evolutionarily robust anti-biofilm strategy. Nat. Commun. 11, 1–11 (2020).
Brown, S. P., West, S. A., Diggle, S. P. & Griffin, A. S. Social evolution in micro-organisms and a Trojan horse approach to medical intervention strategies. Philos. Trans. R. Soc. B Biol. Sci. 364, 3157–3168 (2009).
Gurney, J., Simonet, C., Wollein Waldetoft, K. & Brown, S. P. Challenges and opportunities for cheat therapy in the control of bacterial infections. Nat. Prod. Rep. 39, 325–334 (2022).
Lin, D. M., Koskella, B. & Lin, H. C. Phage therapy: an alternative to antibiotics in the age of multi-drug resistance. World J. Gastrointest. Pharmacol. Ther. 8, 162 (2017).
Atterbury, R. J. & Tyson, J. Predatory bacteria as living antibiotics — Where are we now? Microbiol 167, 1–8 (2021).
Torres-Barceló, C. The disparate effects of bacteriophages on antibiotic-resistant bacteria. Emerg. Microbes Infect. https://doi.org/10.1038/s41426-018-0169-z (2018).
Chan, B. K. et al. Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa. Sci. Rep. 6, 1–8 (2016).
Roemhild, R. & Andersson, D. I. Mechanisms and therapeutic potential of collateral sensitivity to antibiotics. PLoS Pathog. 17, e1009172 (2021).
The authors thank E. Granato, R. Wheatley, C. Sharp and M. Brockhurst for their helpful comments on the manuscript, and M. Jahn, C. Souque, E. Bakkeren, F. Spragge, J. Palmer, S. Booth, O. Cunrath, C. Maclean and L. Comstock for their literature suggestions. C.D.N. is supported by the Simons Foundation (award number 826672), NSF grant IOS 2017879, and grant RGY0077/2020 from the Human Frontier Science Program. B.R.W. received support from a Gillman Fellowship from the Department of Biological Sciences at Dartmouth. W.P.J.S. and K.R.F. are supported by the NIH (project numbers R01AI093771 and R01AI120633), by European Research Council Grant 787932, and by Wellcome Trust Investigator award 209397/Z/17/Z. W.P.J.S. is also funded by a Sir Henry Wellcome Postdoctoral fellowship award, 222795/Z/21/Z.
The authors declare no competing interests.
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Substances (particularly toxins and injected viral DNA) that, through interaction with targets, produce harm to a bacterial cell.
(Phages). Viruses that infect bacteria.
Densely packed cell groups that can contain billions or trillions of cells, enveloped by a secreted extracellular matrix.
Medicine that is derived from (and often incorporating) biological entities. Phages are a potential biotherapeutic for treating bacterial infections.
- Collective defence
Any defensive behaviour that becomes more effective when many individuals engage in it. Collective defences benefit the social partners of a focal bacterium, but do not always evolve for this reason.
- Competition sensing
The bacterial behaviour of discerning and responding to stress cues associated with competitor activity, often via stress responses. This is often used to regulate defences, especially counter-attacks.
Another type of bacterium that competes with a focal bacterium for resources. Often this will be a genetically similar but non-identical bacterium (for example, a different strain), as similar bacteria are most likely to have overlapping resource needs. Genetically identical organisms compete in an ecological sense, but not in an evolutionary sense (as they have the same evolutionary interests). In this Review, we use the term in the former sense.
Aggressions in response to aggression (apparent or actual).
- Danger sensing
Conceptually similar to competition sensing, but pertaining to cues other than those resulting from direct harm to a focal cell.
- Defence mechanisms
Traits that evolved, at least in part, to protect an organism against a threat. This term is often used in the context of bacterial defences against viral threats, but in this Review, we expand it to encompass protection against competitors and predators.
- Exploitative competition
Mutually harmful interactions between bacteria, stemming from competition for contested resources (for example, space or nutrients). Contrasts with interference competition, in which harm is inflicted more directly via weaponry or other means.
- Horizontal gene transfer
(HGT). The flow of genetic information between two organisms, other than that which occurs via reproduction (vertical gene transfer).
A mutually beneficial evolutionary relationship between two organisms — that is, one in which the fitness of each party is improved by the presence of the other.
An evolutionary relationship between two organisms in which one benefits at the expense of the other. In contrast to predators, parasites are generally smaller than and physically associated with the organisms they exploit.
- Plastic responses
Regulated changes to bacterial phenotypes in response to environmental change. Plasticity does not result from genetic change (though it may be genetically encoded).
Phenomenon whereby one gene simultaneously affects multiple traits. Through pleiotropy, a defensive adaptation may affect the phenotype of a bacterium in unexpected ways (for example, by reducing its fitness in the absence of a threat).
Evolutionary adaptations that serve different purposes from the purpose for which they first evolved. For instance, many modern efflux pumps function to remove antibiotics from bacterial cells, but homologous structures probably served different functions (for example, metabolite export) in ancestral strains.
Organisms that consume others for food, killing them in the process.
- Quorum sensing
A widespread density-sensing mechanism found in bacteria and other microbes. Bacteria probe their effective density by secreting small molecules (autoinducers), which stimulate their own production. High autoinducer concentrations then become a proxy for high cell density or for restrictive spatial constraints that limit autoinducer diffusion. Quorum sensing is often used to regulate costly traits the benefits of which depend on collective action.
- Stress responses
A set of regulatory pathways found in bacteria that alter gene expression and cell physiology in response to harmful environmental changes and help the bacteria to survive stress.
Changes in environmental or physiological conditions that perturb cell homeostasis.
Cellular systems that evolved, at least in part, to harm other organisms.
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Smith, W.P.J., Wucher, B.R., Nadell, C.D. et al. Bacterial defences: mechanisms, evolution and antimicrobial resistance. Nat Rev Microbiol (2023). https://doi.org/10.1038/s41579-023-00877-3