Differential contribution of AcrAB and OqxAB efflux pumps to multidrug resistance and virulence in Klebsiella pneumoniae

Bialek-Davenet, Suzanne; Lavigne, Jean‐Philippe; Guyot, Kathleen; Mayer, Noémie; Tournebize, Régis; Brisse, Sylvain; Leflon‐Guibout, Véronique; Nicolas–Chanoine, Marie–Hélène

doi:10.1093/jac/dku340

Cited by 102 publications

(87 citation statements)

References 42 publications

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“…Furthermore, the acrB deletion mutant was more sensitive to exposure to human bronchoalveolar lavage fluid and antimicrobial peptides such as HBD-1 and HBD-2, indicating that this protein is needed for protection against antimicrobial humoral components (355). The increased fitness imparted by AcrB is also supported by work in a Caenorhabditis elegans infection model (357). In terms of antibiotic resistance, an acrB deletion strain of K. pneumoniae is more susceptible than the WT to certain antibiotics such as ␤-lactams (355).…”

Section: Pumps and Transportersmentioning

confidence: 87%

“…AcrAB is an efflux pump that has been implicated in both K. pneumoniae virulence and resistance to antibiotics (355)(356)(357). This contribution to virulence was demonstrated in a mouse model of pneumonic infection, where infection with an acrB deletion mutant in a K2-expressing K. pneumoniae strain resulted in a decreased bacterial load in the lungs compared to that with the WT strain, demonstrating that AcrB enhances bacterial fitness in the lungs (355).…”

Section: Pumps and Transportersmentioning

confidence: 97%

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Klebsiella pneumoniae: Going on the Offense with a Strong Defense

Paczosa

Mecsas

2016

Microbiol Mol Biol Rev

1,357

1,345

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SUMMARYKlebsiella pneumoniaecauses a wide range of infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Historically,K. pneumoniaehas caused serious infection primarily in immunocompromised individuals, but the recent emergence and spread of hypervirulent strains have broadened the number of people susceptible to infections to include those who are healthy and immunosufficient. Furthermore,K. pneumoniaestrains have become increasingly resistant to antibiotics, rendering infection by these strains very challenging to treat. The emergence of hypervirulent and antibiotic-resistant strains has driven a number of recent studies. Work has described the worldwide spread of one drug-resistant strain and a host defense axis, interleukin-17 (IL-17), that is important for controlling infection. Four factors, capsule, lipopolysaccharide, fimbriae, and siderophores, have been well studied and are important for virulence in at least one infection model. Several other factors have been less well characterized but are also important in at least one infection model. However, there is a significant amount of heterogeneity inK. pneumoniaestrains, and not every factor plays the same critical role in all virulentKlebsiellastrains. Recent studies have identified additionalK. pneumoniaevirulence factors and led to more insights about factors important for the growth of this pathogen at a variety of tissue sites. Many of these genes encode proteins that function in metabolism and the regulation of transcription. However, much work is left to be done in characterizing these newly discovered factors, understanding how infections differ between healthy and immunocompromised patients, and identifying attractive bacterial or host targets for treating these infections.

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Section: Pumps and Transportersmentioning

confidence: 87%

Section: Pumps and Transportersmentioning

confidence: 97%

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

Paczosa

Mecsas

2016

Microbiol Mol Biol Rev

1,357

1,345

View full text Add to dashboard Cite

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“…The expression of OqxAB is additionally downregulated by a GntR-type regulator, OqxR, encoded by a gene located downstream of oqxAB (790). A point mutation in oqxR was linked to the hyperexpression of rarA and oqxB (792). Intriguingly, the genetic arrangement of rarA-oqxAB-oqxR is observed both in chromosomes and on a plasmid (790).…”

Section: K Pneumoniae Efflux Pumpsmentioning

confidence: 99%

“…In E. cloacae, inactivation of either acrA or tolC led to reduced fitness (both in vitro and in vivo) as well as reduced virulence in a mouse model of systemic infection (264). A deficiency in AcrAB and OqxAB in K. pneumoniae also caused reduced virulence (792). Similarly, a mutant of V. cholerae deficient in RND pumps pro-duced significantly less cholera toxin and fewer toxin-coregulated pili (341,344), and TolC mutants were deficient in intestinal colonization in mice (917) (but see the comment above on S. enterica serovar Typhimurium).…”

Section: Fitness Colonization and Virulencementioning

confidence: 99%

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

2015

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SUMMARY The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps.

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“…Complete nucleotide sequencing of the oqxAB-carrying plasmid pOLA52, which was isolated from an Escherichia coli strain in 2003, has revealed the genetic environment of plasmid-mediated oqxAB (8). This efflux pump operon, together with the local repressor gene oqxR, was found to be flanked by the insertion sequence IS26, forming a 6,731-bp transposon known as Tn6010 (8,9). Currently, the plasmid-borne oqxAB operon identified in E. coli and Salmonella spp.…”

mentioning

confidence: 99%

IncHI2 Plasmids Are the Key Vectors Responsible for oqxAB Transmission among Salmonella Species

Wong

Chan

Xie

et al. 2016

Antimicrob Agents Chemother

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cThis study reported and analyzed the complete sequences of two oqxAB-bearing IncHI2 plasmids harbored by a clinical Salmonella enterica serovar Typhimurium strain and an S. Indiana strain of animal origin, respectively. In particular, pA3T recovered from S. Indiana comprised the resistance determinants oqxAB, aac(6=)Ib-cr, fosA3, and bla CTX-M-14 . Further genetic screening of 63 oqxAB-positive Salmonella isolates revealed that the majority carried IncHI2 plasmids, confirming that such plasmids play a pivotal role in dissemination of oqxAB in Salmonella spp.

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Differential contribution of AcrAB and OqxAB efflux pumps to multidrug resistance and virulence in Klebsiella pneumoniae

Cited by 102 publications

References 42 publications

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

IncHI2 Plasmids Are the Key Vectors Responsible for oqxAB Transmission among Salmonella Species

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