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Functional and structural diversity in deubiquitinases of the Chlamydia-like bacterium Simkania negevensis
Intracellular bacteria use deubiquitinase effectors to avoid being targeted for autophagic clearance. The authors show that the Chlamydia-like bacterium Simkania negevensis encodes an unusually broad range of these enzymes, including members that specifically target linear and K6-linked ubiquitin chains.
- Vanessa Boll
- , Thomas Hermanns
- & Kay Hofmann
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| Open Access
SIgA structures bound to Streptococcus pyogenes M4 and human CD89 provide insights into host-pathogen interactions
Here, the authors used cryo-EM to explore secretory Immunoglobulin A interactions with bacterial and host receptors, uncovering unexpected binding stoichiometry and unappreciated functional consequences relevant to understanding host-pathogen interactions.
- Qianqiao Liu
- & Beth M. Stadtmueller
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| Open Access
Legionella para-effectors target chromatin and promote bacterial replication
Legionella pneumophilia is known to secrete more than 300 effectors via a type IV secretion system. Here, Schator et al. characterise how the chromatin modifying effectors RomA and LphD work synergistically to hijack host responses and facilitate bacterial replication.
- Daniel Schator
- , Sonia Mondino
- & Monica Rolando
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| Open Access
Mechanism of antibody-specific deglycosylation and immune evasion by Streptococcal IgG-specific endoglycosidases
Bacterial pathogens have evolved intricate mechanisms to evade the human immune system, including the production of immunomodulatory enzymes. Here, the authors establish the mechanisms of recognition and specific deglycosylation of IgG antibodies by the multi-modular enzymes EndoS and EndoS2
- Beatriz Trastoy
- , Jonathan J. Du
- & Marcelo E. Guerin
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| Open Access
Extracellular fibrinogen-binding protein released by intracellular Staphylococcus aureus suppresses host immunity by targeting TRAF3
Staphylococcus aureus secrete numerous effectors to evade or inhibit the host immune response, yet the mechanism underlying the effectors ability to manipulate the signalling pathways of macrophages remain unclear. Authors utilise in vitro and in vivo models to explore the role of extracellular fibrinogen-binding protein (Efb) in immune response modulation and pathogenicity.
- Xiaokai Zhang
- , Tingrong Xiong
- & Quanming Zou
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| Open Access
Streptococcus agalactiae cadD alleviates metal stress and promotes intracellular survival in macrophages and ascending infection during pregnancy
Perinatal infection with Group B Streptococcus (GBS) is associated with preterm birth, neonatal sepsis, and stillbirth. Here, Korir et al. show that gene cadD, encoding a putative metal efflux transporter, is important for metal detoxification, immune evasion and bacterial proliferation in the pregnant host.
- Michelle L. Korir
- , Ryan S. Doster
- & Jennifer A. Gaddy
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| Open Access
Inhibition of the Niemann-Pick C1 protein is a conserved feature of multiple strains of pathogenic mycobacteria
Lipids shed by pathogenic mycobacteria have been shown to inhibit NPC1, a lysosomal membrane protein deficient in most cases of a rate inherited lysosomal storage disorder Niemann-Pick disease type C (NPC). Here, authors utilise lipid extracts from clinical Mycobacterium tuberculosis strains, and non-tubercular mycobacteria to investigate their ability to inhibit the NPC pathway.
- Yuzhe Weng
- , Dawn Shepherd
- & Frances M. Platt
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| Open Access
CrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT
Pseudomonas aeruginosa secretes the toxin ExoT, which is important for pathogenesis. Here, the authors show that ExoT inhibits NLRC4-dependent inflammatory responses during wound infection.
- Mohamed F. Mohamed
- , Kajal Gupta
- & Sasha H. Shafikhani
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| Open Access
Rough and smooth variants of Mycobacterium abscessus are differentially controlled by host immunity during chronic infection of adult zebrafish
The pathogen Mycobacterium abscessus can switch from a smooth colony form (S) into a highly inflammatory, rough colony form (R) during infection. Here, Kam et al. use an adult zebrafish model of M. abscessus chronic infection to illustrate differences in the immunopathogenesis induced by R and S variants.
- Julia Y. Kam
- , Elinor Hortle
- & Stefan H. Oehlers
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Article
| Open Access
Translocated Legionella pneumophila small RNAs mimic eukaryotic microRNAs targeting the host immune response
Legionella pneumophila expresses a range of bacterial determinants that mimic eukaryotic functions. Here the authors show small RNAs of L.pneumophila mimic eukaryotic microRNA and modulate the host response to infection.
- Tobias Sahr
- , Pedro Escoll
- & Carmen Buchrieser
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Article
| Open Access
Psychological stress impairs IL22-driven protective gut mucosal immunity against colonising pathobionts
Altered gut microbiome and exacerbation of symptoms at times of psychological stress are feature characteristics of Crohn’s disease. Here authors show in a mouse model that psychological stress impairs IL-22-dependent protective immunity of the ileal mucosa, which allows invasive bacteria to colonise the gut.
- Christopher R. Shaler
- , Alexandra A. Parco
- & Brian K. Coombes
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| Open Access
Colonization of dermal arterioles by Neisseria meningitidis provides a safe haven from neutrophils
The human pathogen Neisseria meningitidis colonizes blood vessels and causes vascular damage, despite a neutrophil-rich inflammatory infiltrate. Here, Manriquez et al. use a humanized mouse model to show that pathogen colonization of capillaries and arterioles creates an intravascular niche that precludes an effective action of neutrophils.
- Valeria Manriquez
- , Pierre Nivoit
- & Guillaume Duménil
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| Open Access
Small RNA mediated gradual control of lipopolysaccharide biosynthesis affects antibiotic resistance in Helicobacter pylori
The small RNA RepG modulates expression of chemotaxis receptor TlpB in Helicobacter pylori by targeting a length-variable G-repeat in the tlpB mRNA. Here, Pernitzsch et al. show that RepG also gradually controls lipopolysaccharide biosynthesis, antibiotic susceptibility, and in-vivo colonization of the stomach, by regulating a gene that is co-transcribed with tlpB.
- Sandy R. Pernitzsch
- , Mona Alzheimer
- & Cynthia M. Sharma
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| Open Access
Structural basis of the membrane intramolecular transacylase reaction responsible for lyso-form lipoprotein synthesis
In Gram-positive bacteria, lipoprotein intramolecular transacylase Lit produces a lipoprotein variant with less immunogenicity. As such, Lit can be viewed as a virulence factor. Here, structural and functional characterization of the enzyme provides insight into its catalytic mechanism, setting the stage for future studies of Lit as a target for new antibiotics.
- Samir Olatunji
- , Katherine Bowen
- & Martin Caffrey
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Article
| Open Access
TcpC inhibits neutrophil extracellular trap formation by enhancing ubiquitination mediated degradation of peptidylarginine deiminase 4
TcpC is a well characterised multifunctional virulence factor expressed by uropathogenic Eschericia coli. Here the authors show that TcpC also targets neutrophil NETosis via its E3 ligase functionality promoting the degradation of PAD4, and represents an additional immune evasion function of this bacterially derived virulence factor.
- Qian Ou
- , Jia-qi Fang
- & Jian-ping Pan
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| Open Access
Staphylococcus aureus induces an itaconate-dominated immunometabolic response that drives biofilm formation
The authors show that the pathogen Staphylococcus aureus induces a distinct airway immunometabolic response, dominated by release of itaconate. This metabolite, in turn, potentiates extracellular polysaccharide synthesis and biofilm formation in S. aureus, which may facilitate chronic infection.
- Kira L. Tomlinson
- , Tania Wong Fok Lung
- & Sebastián A. Riquelme
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| Open Access
Extracellular bacterial lymphatic metastasis drives Streptococcus pyogenes systemic infection
Pathogenic agents can spread from an initial to a secondary site via the lymphatics. Here, using a mouse model of infection, the authors show that S. pyogenes readily transit through sequential lymph nodes within efferent lymphatics to reach the bloodstream and drive systemic infection, while remaining extracellular.
- Matthew K. Siggins
- , Nicola N. Lynskey
- & Shiranee Sriskandan
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| Open Access
“Gene accordions” cause genotypic and phenotypic heterogeneity in clonal populations of Staphylococcus aureus
Gene tandem amplifications can drive bacterial evolution. Here, Belikova et al. identify copy number variations of lipoprotein-encoding genes in Staphylococcus aureus clinical isolates, and show that the loci expand and contract during bacterial growth in vitro and in mice, leading to changes in immunostimulatory capacity.
- Darya Belikova
- , Angelika Jochim
- & Simon Heilbronner
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| Open Access
High-throughput screen reveals sRNAs regulating crRNA biogenesis by targeting CRISPR leader to repress Rho termination
Small non-coding RNAs (sRNA) regulate bacterial functions by finding nucleic acids and proteins. Here the authors identify PhrS sRNA in Pseudomonas as a positive regulator of CRISPR, and show PhrS acts by binding to CRISPR leader, thereby preventing Rho-mediated transcription termination and promoting anti-bacteriophage immunity.
- Ping Lin
- , Qinqin Pu
- & Min Wu
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| Open Access
Hydrogen peroxide release by bacteria suppresses inflammasome-dependent innate immunity
The functions of microbial hydrogen peroxide (H2O2) in host-pathogen interactions are unclear. Here, Erttmann and Gekara show that H2O2 released by Streptococcus pneumoniae inhibits inflammasomes, and thereby contributes to the pathogen’s ability to colonize the host.
- Saskia F. Erttmann
- & Nelson O. Gekara
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| Open Access
Lipid moieties on lipoproteins of commensal and non-commensal staphylococci induce differential immune responses
The Lpp lipoproteins of staphylococci trigger a TLR2-dependent immune response. Here, the authors show that commensal species (S. aureus, S. epidermidis) induce a less-intense TLR2 response than non-commensal species (S. carnosus) due to differential modification of the Lpp lipid moieties.
- Minh-Thu Nguyen
- , Julia Uebele
- & Friedrich Götz
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| Open Access
Dynamic capsule restructuring by the main pneumococcal autolysin LytA in response to the epithelium
Pneumococci produce a carbohydrate capsule that protects them against components of the host immune system but sensitizes them to host antimicrobial peptides. Here, Kietzman et al.show that pneumococci respond to antimicrobial peptides by capsule shedding, which requires the main autolysin LytA.
- Colin C. Kietzman
- , Geli Gao
- & Elaine I. Tuomanen
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| Open Access
A biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable Haemophilus influenzae
Non-typeable Haemophilus influenzae, which causes ear and lung infections, has a DNA methyltransferase encoded by alternative alleles that are subject to random ON/OFF switching. Here, Atack et al.show that this epigenetic switch controls the expression of key proteins involved in virulence.
- John M. Atack
- , Yogitha N. Srikhanta
- & Michael P. Jennings
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The staphylococcal toxins γ-haemolysin AB and CB differentially target phagocytes by employing specific chemokine receptors
Genes encoding two pore-forming toxins (γ-haemolysins HlgAB and HlgCB) are present in almost all human Staphylococcus aureus isolates. Here Spaan et al.show that HlgAB and HlgCB target different phagocyte types by interacting with specific chemokine receptors and complement receptors, respectively.
- András N. Spaan
- , Manouk Vrieling
- & Thomas Henry
Cryo-EM structures of type IV pili complexed with nanobodies reveal immune escape mechanisms