The Contribution of Antibiotic Resistance Mechanisms in Clinical Burkholderia cepacia Complex Isolates: An Emphasis on Efflux Pump Activity

Tseng, Sung-Pin; Tsai, Wan–Chi; Liang, Chih-Yuan; Lin, Yin-Shiou; Huang, Junwei; Chang, Chih-Yuan; Tyan, Yu‐Chang; Lu, Po‐Liang

doi:10.1371/journal.pone.0104986

Cited by 48 publications

(45 citation statements)

References 36 publications

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“…High-level ciprofloxacin resistance (MIC>256 μg/ml) required an additional Ser80Leu mutation in the ParC QRDR (Pope et al, 2008). Similar gyrA mutations were identified in a majority of levofloxacin resistant isolates studied in a survey of resistance mechanisms in Bcc (Tseng et al, 2014). The resistant isolates contained Gly81Asp, Thr83Ile, and Asp87His mutations.…”

Section: Burkholderia Cepacia Complex Organismssupporting

confidence: 59%

“…Of these RND-3, RND-4, and RND-10 (also known as CeoAB-OpcM) correspond to B. pseudomallei AmrAB-OprA, BpeAB-OprB and BpeEF-OprC, respectively, although the resistance patterns bestowed by the respective pumps are somewhat different, with the exception of RND-10 and BpeEF-OprC whose resistance profiles are very similar (Podnecky et al, 2015). An inventory of B. cenocepacia resistance mechanisms showed that efflux pump activity is prevalent in this bacterium and that mutations in the RND-3 pump regulator are the major cause of efflux pump activity and RND-3 mediated antibiotic resistance (Tseng et al, 2014). In B. vietnamiensis , aminoglycoside resistance emerges during chronic infection or after in vitro exposure to aminoglycosides and is the result of AmrAB-OprM efflux pump expression, which is most likely a homolog of B. pseudomallei and B. thailandensis AmrAB-OprA (Jassem et al, 2014; Jassem et al, 2011).…”

Section: Burkholderia Cepacia Complex Organismsmentioning

confidence: 99%

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Antibiotic resistance in Burkholderia species

Rhodes

Schweizer

2016

Drug Resistance Updates

280

256

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The genus Burkholderia comprises metabolically diverse and adaptable Gram-negative bacteria, which thrive in often adversarial environments. A few members of the genus are prominent opportunistic pathogens. These include B. mallei and B. pseudomallei of the B. pseudomallei complex, which cause glanders and melioidosis, respectively. B. cenocepacia, B. multivorans, and B. vietnamiensis belong to the B. cepacia complex and affect mostly cystic fibrosis patients. Infections caused by these bacteria are difficult to treat because of significant antibiotic resistance. The first line of defense against antimicrobials in Burkholderia species is the outer membrane penetration barrier. Most Burkholderia contain a modified lipopolysaccharide that causes intrinsic polymyxin resistance. Contributing to reduced drug penetration are restrictive porin proteins. Efflux pumps of the resistance nodulation cell division family are major players in Burkholderia multidrug resistance. Third and fourth generation β-lactam antibiotics are seminal for treatment of Burkholderia infections, but therapeutic efficacy is compromised by expression of several β-lactamases and ceftazidime target mutations. Altered DNA gyrase and dihydrofolate reductase targets cause fluoroquinolone and trimethoprim resistance, respectively. Although antibiotic resistance hampers therapy of Burkholderia infections, the characterization of resistance mechanisms lags behind other non-enteric Gram-negative pathogens, especially ESKAPE bacteria such as Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa.

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Section: Burkholderia Cepacia Complex Organismssupporting

confidence: 59%

Section: Burkholderia Cepacia Complex Organismsmentioning

confidence: 99%

Antibiotic resistance in Burkholderia species

Rhodes

Schweizer

2016

Drug Resistance Updates

280

256

View full text Add to dashboard Cite

show abstract

“…With 16 RND pumps present in B. cenocepacia strain J2315, their differential roles in drug resistance of planktonic and biofilm cells were investigated (613). Another study showed the high prevalence of RND pump-overproducing clinical isolates (particularly RND-3 overproducers) (616). However, the data regarding the effect of PA␤N on antibi-otic susceptibility appeared contradictory.…”

Section: Burkholderia Sppmentioning

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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“…The genome of another CF pathogen, B. cenocepacia, contains genes coding for 22 RND efflux systems (37)(38)(39)(40), and high levels of expression of these efflux pumps are frequently observed in B. cepacia complex clinical isolates (41). Exposure of B. cenocepacia biofilms to the disinfectant chlorhexidine results in the up-regulation of eight RND family efflux pumps (42).…”

Section: Burkholderia Cenocepaciamentioning

confidence: 99%

The Role of Efflux and Physiological Adaptation in Biofilm Tolerance and Resistance

Acker

Coenye

2016

Journal of Biological Chemistry

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Microbial biofilms demonstrate a decreased susceptibility to antimicrobial agents. Various mechanisms have been proposed to be involved in this recalcitrance. We focus on two of these factors. Firstly, the ability of sessile cells to actively mediate efflux of antimicrobial compounds has a profound impact on resistance and tolerance, and several studies point to the existence of biofilm-specific efflux systems. Secondly, biofilm-specific stress responses have a marked influence on cellular physiology, and contribute to the occurrence of persister cells. We provide an overview of the data that demonstrate that both processes are important for survival following exposure to antimicrobial agents.Microbial biofilms are surface-attached communities, consisting of cells embedded in an extracellular polymeric matrix that is at least partially composed of polymers produced by the microorganism themselves (1). Biofilms are omnipresent in natural and man-made environments (1, 2), and biofilm-associated bacteria are involved in a wide range of infections, including respiratory tract infections in cystic fibrosis (CF) 2 patients, chronically infected wounds, and device-related infections (3, 4). One of the hallmarks of these biofilm-associated infections is the frequent failure of antimicrobial chemotherapy. Although it is often postulated that sessile cells are more resistant to antimicrobial agents, these cells typically do not grow better than planktonic cells in the presence of antibiotics; for example, biofilm-associated and stationary-phase planktonic Burkholderia cepacia complex bacteria showed similar susceptibilities to antibiotics (5). However, it is much more difficult to kill biofilm-associated cells than planktonic cells (6), and various mechanisms that potentially could be involved in this have been described in the literature (see Refs. 7 and 8 for recent reviews as well as Refs. 9 and 10 in this minireview series). Avoiding exposure to (sufficiently high concentrations of) antibiotics, and the presence of a small population of specialized survivor cells that are tolerant toward particular antimicrobial agents (i.e. they are not killed upon exposure to the product) are two important mechanisms that will be discussed in this review.

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The Contribution of Antibiotic Resistance Mechanisms in Clinical Burkholderia cepacia Complex Isolates: An Emphasis on Efflux Pump Activity

Cited by 48 publications

References 36 publications

Antibiotic resistance in Burkholderia species

Antibiotic resistance in Burkholderia species

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

The Role of Efflux and Physiological Adaptation in Biofilm Tolerance and Resistance

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