Prokaryotic membrane vesicles: new insights on biogenesis and biological roles

Haurat, M. Florencia; Elhenawy, Wael; Feldman, Mario F.

doi:10.1515/hsz-2014-0183

Cited by 121 publications

(130 citation statements)

References 116 publications

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“…The protein composition of OMVs is known to differ from that of the source outer membrane. The contents of OMVs are known to be selectively packaged, enriching in molecules that may impact inflammation (20,34). Therefore, we tested the proinflammatory cytokine responses of macrophages exposed to enriched total outer membrane from strains expressing neither porin, either porin, or both porins to determine if the responses were similar.…”

Section: Resultsmentioning

confidence: 99%

Porin Loss Impacts the Host Inflammatory Response to Outer Membrane Vesicles of Klebsiella pneumoniae

Turner

Cahill

Dilello

et al. 2016

Antimicrob Agents Chemother

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Antibiotic-resistant strains of Klebsiella pneumoniae often exhibit porin loss. In this study, we investigated how porin loss impacted the composition of secreted outer membrane vesicles as well as their ability to trigger proinflammatory cytokine secretion by macrophages. We hypothesize that porin loss associated with antibiotic resistance will directly impact both the composition of outer membrane vesicles and their interactions with phagocytic cells. Using clonally related clinical isolates of extended-spectrum beta-lactamase (ESBL)-positive Klebsiella pneumoniae with different patterns of porin expression, we demonstrated that altered expression of OmpK35 and OmpK36 results in broad alterations to the protein profile of secreted vesicles. Additionally, the level of OmpA incorporation was elevated in strains lacking a single porin. Porin loss significantly impacted macrophage inflammatory responses to purified vesicles. Outer membrane vesicles lacking both OmpK35 and OmpK36 elicited significantly lower levels of proinflammatory cytokine secretion than vesicles from strains expressing one or both porins. These data demonstrate that antibiotic resistance-associated porin loss has a broad and significant effect on both the composition of outer membrane vesicles and their interactions with phagocytic cells, which may impact bacterial survival and inflammatory reactions in the host.K lebsiella pneumoniae is a nosocomial pathogen responsible for as many as 20% of all cases of culture-positive blood cultures and bacterial sepsis (1). Alarmingly, up to 50% of these infections are resistant to most current antibiotics (2, 3). The majority of resistant Klebsiella isolates exhibit both expression of an extendedspectrum beta-lactamase (ESBL) and halted expression of at least one outer membrane porin (4, 5). Porin loss has been clearly shown to enhance levels of antibiotic resistance, and ESBL-positive K. pneumoniae isolates commonly exhibit loss of OmpK35 and OmpK36, which both function in nonspecific transport across the outer membrane (6-8).While changes to the porin profile of bacteria are well documented to be associated with enhanced antibiotic resistance (9, 10), the role that these porins play in pathogenesis has not been fully investigated. In vitro experiments using mutants of K. pneumoniae lacking OmpK36 have demonstrated that loss of OmpK36 results in increased phagocytic killing of the bacteria, and in vivo experiments have demonstrated decreased virulence and bacterial survival of strains lacking OmpK36 in a mouse model (11)(12)(13)(14). Data from these studies consistently indicate that loss of OmpK36 results in an increase in antibiotic resistance paired with a decrease in fitness and ability to survive host immune responses. It is unclear how resistant strains of Klebsiella are able to persist in host tissues when porin loss renders the bacteria more susceptible to phagocytic clearance.The capsule is the best understood of the virulence factors of Klebsiella, cloaking the bacterial outer surface from immu...

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Section: Resultsmentioning

confidence: 99%

Porin Loss Impacts the Host Inflammatory Response to Outer Membrane Vesicles of Klebsiella pneumoniae

Turner

Cahill

Dilello

et al. 2016

Antimicrob Agents Chemother

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“…A special case of protein secretion is the production of outer membrane vesicles (OMVs), which are blebs of outer membrane (OM) released from the bacterial cell surface (94). There is significant debate regarding whether OMVs are produced by a directed process or simply represent cellular debris.…”

Section: Protein Secretionmentioning

confidence: 99%

“…There is significant debate regarding whether OMVs are produced by a directed process or simply represent cellular debris. Proteomic comparisons between the OM and OMVs of some bacteria have shown that the protein profiles differ between these two fractions, indicating that some OM proteins are excluded from OMV recruitment and suggesting that OMV formation is a directed process (94). However, many studies also detected cytoplasmic proteins in OMV preparations, indicating that cell lysis could also be a major contributor to OMV formation (94).…”

Section: Protein Secretionmentioning

confidence: 99%

“…Proteomic comparisons between the OM and OMVs of some bacteria have shown that the protein profiles differ between these two fractions, indicating that some OM proteins are excluded from OMV recruitment and suggesting that OMV formation is a directed process (94). However, many studies also detected cytoplasmic proteins in OMV preparations, indicating that cell lysis could also be a major contributor to OMV formation (94). OMVs have been implicated in numerous biological functions, with particular attention being devoted to their role in virulence (95).…”

Section: Protein Secretionmentioning

confidence: 99%

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Pathogenic Acinetobacter: from the Cell Surface to Infinity and Beyond

2016

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The genus Acinetobacter encompasses multiple nosocomial opportunistic pathogens that are of increasing worldwide relevance because of their ability to survive exposure to various antimicrobial and sterilization agents. Among these, Acinetobacter baumannii, Acinetobacter nosocomialis, and Acinetobacter pittii are the most frequently isolated in hospitals around the world. Despite the growing incidence of multidrug-resistant Acinetobacter spp., little is known about the factors that contribute to pathogenesis. New strategies for treating and managing infections caused by multidrug-resistant Acinetobacter strains are urgently needed, and this requires a detailed understanding of the pathobiology of these organisms. In recent years, some virulence factors important for Acinetobacter colonization have started to emerge. In this review, we focus on several recently described virulence factors that act at the bacterial surface level, such as the capsule, O-linked protein glycosylation, and adhesins. Furthermore, we describe the current knowledge regarding the type II and type VI secretion systems present in these strains.

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“…It has been long proposed that such mechanisms could be a bacterial strategy to release proteins in the extracellular medium, proteins that will then be packaged in these vesicles [267]. One major issue with this, of course, is to determine whether there is any level of specificity in the process or whether vesicles engulf whatever is there.…”

Section: Om Vesiclesmentioning

confidence: 99%