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Implant infections: adhesion, biofilm formation and immune evasion

Abstract

Medical device-associated infections account for a large proportion of hospital-acquired infections. A variety of opportunistic pathogens can cause implant infections, depending on the type of the implant and on the anatomical site of implantation. The success of these versatile pathogens depends on rapid adhesion to virtually all biomaterial surfaces and survival in the hostile host environment. Biofilm formation on implant surfaces shelters the bacteria and encourages persistence of infection. Furthermore, implant-infecting bacteria can elude innate and adaptive host defences as well as biocides and antibiotic chemotherapies. In this Review, we explore the fundamental pathogenic mechanisms underlying implant infections, highlighting orthopaedic implants and Staphylococcus aureus as a prime example, and discuss innovative targets for preventive and therapeutic strategies.

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Fig. 1: Adhesion of Staphylococcus aureus to implant surfaces.
Fig. 2: Stages of staphylococcal biofilm formation.
Fig. 3: Immune evasion by Staphylococcus aureus.

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Acknowledgements

The authors gratefully acknowledge M. P. Landini for the inspiring atmosphere at the Rizzoli Orthopaedic Institute. This work was supported by the POR-FESR 2014–2020 grant (Project No. 725827) and by the “5 per mille” grants to the Rizzoli Orthopaedic Institute.

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Glossary

Health-care-associated infections

An infection contracted by a patient while receiving medical care in a hospital or in another health-care facility (synonymous with nosocomial and hospital infection).

Opportunistic pathogens

Microorganisms that generally live harmlessly as commensals but can cause infection in hosts with lowered resistance to disease.

Granulation tissue

New connective tissue and capillaries that replace the fibrin matrix during wound healing.

Coagulase-negative staphylococci

(CNS). A broad group of staphylococci devoid of coagulase activity that includes some of the staphylococcal species that often cause hospital-acquired infections.

Total arthroplasty

A reconstructive surgical procedure consisting of replacement of a joint with an artificial prosthesis.

Wettability

Ability of a solid surface to reduce the surface tension of a liquid in contact with it so that the liquid spreads over the surface and wets it.

Extended Derjaguin–Landau–Verwey–Overbeek theory

(XDLVO theory). A theory that describes the interactions between material surfaces immersed in a liquid, taking into account the different attractive and repulsive forces (Lifshitz–van der Waals, electrical double layer and Lewis acid–base forces). It can be used to predict the interactions of bacteria and biomaterial surfaces.

Conjugation

A mechanism by which genetic material can transfer between bacterial cells. It involves direct cell-to-cell contact or a bridge-like connection between cells.

Quorum sensing system

A bacterial regulatory system based on signalling molecules (autoinducers) that reflect bacterial cell-population density and regulate gene expression in response to it.

Surfactant molecules

Compounds that lower the surface tension between two liquids or between a liquid and a solid.

Non-professional phagocytes

A variety of non-immune cells that are capable of phagocytosis, including fibroblasts, osteoblasts, keratinocytes and endothelial cells.

Professional phagocytes

A group of cells that includes phagocytes of the innate immune system, such as neutrophils, monocytes, macrophages, mast cells and dendritic cells.

Small colony variant

Slow-growing variant of bacteria that arises spontaneously and forms small colonies when grown in the laboratory. These variants are implicated in persistent infections.

Canaliculi

Thin, hair-like channels in the bone that link the lacunae with one another and with the Haversian canal.

Lacunae

Small cavities within the bone matrix in which single osteocytes are lodged.

ESKAPE pathogens

Acronym for a group of pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species) that are some of the main species that cause antimicrobial-resistant infections.

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Arciola, C.R., Campoccia, D. & Montanaro, L. Implant infections: adhesion, biofilm formation and immune evasion. Nat Rev Microbiol 16, 397–409 (2018). https://doi.org/10.1038/s41579-018-0019-y

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