Inactivation of MuxABC-OpmB transporter system in Pseudomonas aeruginosa leads to increased ampicillin and carbenicillin resistance and decreased virulence

Yang, Liang; Chen, Lin; Shen, Liuhong; Surette, Michael G.; Duan, Kangmin

doi:10.1007/s12275-011-0186-2

Cited by 45 publications

(25 citation statements)

References 58 publications

(75 reference statements)

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“…In response to the infection by P. aeruginosa, the polymorphonuclear leukocytes (PMNs) release reactive oxygen species (ROS) [107] and reactive nitrogen intermediates which, if able to overwhelm the infecting organism, damage the lipids and proteins inside it. However, if unable to do so, mutations in P. aeruginosa will allow for selection of the variants able to sustain these challenges [108].…”

Section: Discussionmentioning

confidence: 99%

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection

et al. 2016

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BackgroundThe airways of patients with cystic fibrosis (CF) are highly complex, subject to various environmental conditions as well as a distinct microbiota. Pseudomonas aeruginosa is recognized as one of the most important pulmonary pathogens and the predominant cause of morbidity and mortality in CF. A multifarious interplay between the host, pathogens, microbiota, and the environment shapes the course of the disease. There have been several excellent reviews detailing CF pathology, Pseudomonas and the role of environment in CF but only a few reviews connect these entities with regards to influence on the overall course of the disease. A holistic understanding of contributing factors is pertinent to inform new research and therapeutics.DiscussionIn this article, we discuss the deterministic alterations in lung physiology as a result of CF. We also revisit the impact of those changes on the microbiota, with special emphasis on P. aeruginosa and the influence of other non-genetic factors on CF. Substantial past and current research on various genetic and non-genetic aspects of cystic fibrosis has been reviewed to assess the effect of different factors on CF pulmonary infection. A thorough review of contributing factors in CF and the alterations in lung physiology indicate that CF lung infection is multi-factorial with no isolated cause that should be solely targeted to control disease progression. A combinatorial approach may be required to ensure better disease outcomes.ConclusionCF lung infection is a complex disease and requires a broad multidisciplinary approach to improve CF disease outcomes. A holistic understanding of the underlying mechanisms and non-genetic contributing factors in CF is central to development of new and targeted therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection

et al. 2016

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“…Several cloned RND pumps were able to confer resistance to a P. aeruginosa or E. coli host deficient in major RND pumps: MexMN-OprM for resistance to macrolides and fluoroquinolones (487); MexPQ-OpmE for resistance to amphenicols (487); MexVW-OprM for resistance to macrolides, chloramphenicol, fluoroquinolones, and tetracycline (488); and MuxABC-OpmB (with two RND components, MuxBC) for resistance to aztreonam, macrolides, novobiocin, and tetracyclines (489). The inactivation of MuxABC-OpmB increases resistance to carbenicillin (490). TriABC-OpmH, with an unusual property of requiring two periplasmic adaptor proteins, TriA and TriB, pumps out triclosan (491), while the CzcCBA (CzrCBA) system is involved in resistance to cadmium, cobalt, and zinc salts (492,493).…”

Section: Pseudomonas Aeruginosamentioning

confidence: 99%

“…Strains coisolated from chronically colonized airways of cystic fibrosis patients contained frequent mutations in mexR that may have resulted in MexAB-OprM overproduction (450). Decreased virulence is associated with MuxABC-OpmB inactivation (490). However, the outcome of P. aeruginosa infections is known to depend primarily upon the patient's conditions, and the contribution of bacterial virulence is sometimes not very clear.…”

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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“…Inactivation of muxA in the muxABC-ompB operon showed attenuated virulence associated with decreased twitching motility and elevated resistance to ampicillin and carbenicillin (151).…”

Section: Resistance To Macrolides and Effect On Virulencementioning

confidence: 99%

Antimicrobial Resistance and Virulence: a Successful or Deleterious Association in the Bacterial World?

Beceiro

Tomás²,

Bou³

2013

Clin Microbiol Rev

857

630

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SUMMARY Hosts and bacteria have coevolved over millions of years, during which pathogenic bacteria have modified their virulence mechanisms to adapt to host defense systems. Although the spread of pathogens has been hindered by the discovery and widespread use of antimicrobial agents, antimicrobial resistance has increased globally. The emergence of resistant bacteria has accelerated in recent years, mainly as a result of increased selective pressure. However, although antimicrobial resistance and bacterial virulence have developed on different timescales, they share some common characteristics. This review considers how bacterial virulence and fitness are affected by antibiotic resistance and also how the relationship between virulence and resistance is affected by different genetic mechanisms (e.g., coselection and compensatory mutations) and by the most prevalent global responses. The interplay between these factors and the associated biological costs depend on four main factors: the bacterial species involved, virulence and resistance mechanisms, the ecological niche, and the host. The development of new strategies involving new antimicrobials or nonantimicrobial compounds and of novel diagnostic methods that focus on high-risk clones and rapid tests to detect virulence markers may help to resolve the increasing problem of the association between virulence and resistance, which is becoming more beneficial for pathogenic bacteria.

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Inactivation of MuxABC-OpmB transporter system in Pseudomonas aeruginosa leads to increased ampicillin and carbenicillin resistance and decreased virulence

Cited by 45 publications

References 58 publications

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection

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

Antimicrobial Resistance and Virulence: a Successful or Deleterious Association in the Bacterial World?

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