Exploring the Interplay of Resistance Nodulation Division Efflux Pumps, AmpC and OprD in Antimicrobial Resistance of Burkholderia cepacia Complex in Clinical Isolates

2020 ◽  
Vol 26 (10) ◽  
pp. 1144-1152
Author(s):  
Vikas Gautam ◽  
Sunil Kumar ◽  
Prashant P. Patil ◽  
Joseph Meletiadis ◽  
Prabhu B. Patil ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Burkholderia Cepacia ◽  
Efflux Pumps ◽  
Clinical Isolates ◽  
Burkholderia Cepacia Complex ◽  
Resistance Nodulation Division

scholarly journals Swimming Motility in a Longitudinal Collection of Clinical Isolates of Burkholderia cepacia Complex Bacteria from People with Cystic Fibrosis

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e106428 ◽  
Author(s):  
James E. A. Zlosnik ◽  
Paul Y. Mori ◽  
Derek To ◽  
James Leung ◽  
Trevor J. Hird ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Burkholderia Cepacia ◽  
Clinical Isolates ◽  
Burkholderia Cepacia Complex ◽  
Swimming Motility

scholarly journals Involvement of the AcrAB-TolC Efflux Pump in the Resistance, Fitness, and Virulence of Enterobacter cloacae

2012 ◽  
Vol 56 (4) ◽  
pp. 2084-2090 ◽  
Author(s):  
Astrid Pérez ◽  
Margarita Poza ◽  
Ana Fernández ◽  
Maria del Carmen Fernández ◽  
Susana Mallo ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Pathogenic Bacteria ◽  
Efflux Pump ◽  
Enterobacter Cloacae ◽  
Efflux Pumps ◽  
Clinical Isolates ◽  
Wild Type ◽  
Content Type

ABSTRACTMultidrug efflux pumps have emerged as important mechanisms of antimicrobial resistance in bacterial pathogens. In order to cause infection, pathogenic bacteria require mechanisms to avoid the effects of host-produced compounds, and express efflux pumps may accomplish this task. In this study, we evaluated the effect of the inactivation of AcrAB-TolC on antimicrobial resistance, fitness, and virulence inEnterobacter cloacae, an opportunistic pathogen usually involved in nosocomial infections. Two different clinical isolates ofE. cloacaewere used, EcDC64 (multidrug resistance overexpressing the AcrAB-TolC efflux pump) and Jc194 (basal AcrAB-TolC expression). TheacrAandtolCgenes were deleted in strains EcDC64 and Jc194 to produce, respectively, EcΔacrAand EcΔtolCand JcΔacrAand JcΔtolCknockout (KO) derivatives. Antibiotic susceptibility testing was performed with all isolates, and we discovered that these mechanisms are involved in the resistance ofE. cloacaeto several antibiotics. Competition experiments were also performed with wild-type and isogenic KO strains. The competition index (CI), defined as the mutant/wild-type ratio, revealed that theacrAandtolCgenes both affect the fitness ofE. cloacae, as fitness was clearly reduced in theacrAandtolCKO strains. The median CI values obtainedin vitroandin vivowere, respectively, 0.42 and 0.3 for EcDC64/EcΔacrA, 0.24 and 0.38 for EcDC64/EcΔtolC, 0.15 and 0.11 for Jc194/JcΔacrA, and 0.38 and 0.39 for Jc194/JcΔtolC. Use of an intraperitoneal mouse model of systemic infection revealed reduced virulence in bothE. cloacaeclinical strains when either theacrAortolCgene was inactivated. In conclusion, the structural components of the AcrAB-TolC efflux pump appear to play a role in antibiotic resistance as well as environmental adaptation and host virulence in clinical isolates ofE. cloacae.

scholarly journals Multidrug Resistance Efflux Pumps in Acinetobacter spp.: An Update

2021 ◽  
Author(s):  
Vanessa Kornelsen ◽  
Ayush Kumar
Keyword(s):  
Multidrug Resistance ◽  
Antimicrobial Resistance ◽  
Bacterial Species ◽  
Clinical Importance ◽  
Efflux Pumps ◽  
Major Facilitator Superfamily ◽  
Small Multidrug Resistance ◽  
Resistance Nodulation Division ◽  
Rnd Efflux Pumps ◽  
Major Facilitator

Acinetobacter spp. have become of increased clinical importance as studies have shown the antimicrobial resistant potential of these species. Efflux pumps can lead to reduced susceptibility to a variety of antibiotics and are present in large number across Acinetobacter spp. There are six families of efflux pumps that have been shown to be of clinical relevance: the Major Facilitator Superfamily (MFS), Small Multidrug Resistance (SMR) family, ATP-binding cassette (ABC) family, Multidrug and Toxic Compound Extrusion (MATE) family, Proteobacterial Antimicrobial Compound Efflux (PACE) family and Resistance-Nodulation-Division (RND) family. A lot of work has been done on understanding and characterizing the roles that these efflux pumps play in relation to antimicrobial resistance and the physiology of these bacteria. RND efflux pumps, with their expansive substrate profiles, are a major component of Acinetobacter spp. antimicrobial resistance. New discoveries over the last decade have shed a lot of light on to the complex regulation of these efflux pumps leading to greater understanding and potential of slowing the reduced susceptibility seen by these bacterial species.

Performance of MALDI-ToF MS for species identification of Burkholderia cepacia complex clinical isolates

2013 ◽  
Vol 77 (2) ◽  
pp. 126-128 ◽  
Author(s):  
Lorena Cristina Corrêa Fehlberg ◽  
Lucas Henrique Sales Andrade ◽  
Diego Magno Assis ◽  
Rosana Helena Vicente Pereira ◽  
Ana Cristina Gales ◽  
...  
Keyword(s):  
Species Identification ◽  
Burkholderia Cepacia ◽  
Clinical Isolates ◽  
Burkholderia Cepacia Complex ◽  
Maldi Tof Ms ◽  
Maldi Tof ◽  
Tof Ms

scholarly journals Importance of Multidrug Efflux Pumps in the Antimicrobial Resistance Property of Clinical Multidrug-Resistant Isolates of Neisseria gonorrhoeae

2014 ◽  
Vol 58 (6) ◽  
pp. 3556-3559 ◽  
Author(s):  
Daniel Golparian ◽  
William M. Shafer ◽  
Makoto Ohnishi ◽  
Magnus Unemo
Keyword(s):  
Antimicrobial Resistance ◽  
Neisseria Gonorrhoeae ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Multidrug Efflux ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Multidrug Efflux Pumps ◽  
Drug Efflux Pumps

ABSTRACTThe contribution of drug efflux pumps in clinical isolates ofNeisseria gonorrhoeaethat express extensively drug-resistant or multidrug-resistant phenotypes has heretofore not been examined. Accordingly, we assessed the effect on antimicrobial resistance of loss of the three gonococcal efflux pumps associated with a known capacity to export antimicrobials (MtrC-MtrD-MtrE, MacA-MacB, and NorM) in such clinical isolates. We report that the MIC of several antimicrobials, including seven previously and currently recommended for treatment was significantly impacted.

scholarly journals Burkholderia ubonensis Meropenem Resistance: Insights into Distinct Properties of Class A β-Lactamases in Burkholderia cepacia Complex and Burkholderia pseudomallei Complex Bacteria

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Nawarat Somprasong ◽  
Carina M. Hall ◽  
Jessica R. Webb ◽  
Jason W. Sahl ◽  
David M. Wagner ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Burkholderia Cepacia ◽  
Burkholderia Pseudomallei ◽  
Carbapenem Resistance ◽  
Near Neighbor ◽  
Burkholderia Cepacia Complex ◽  
Intrinsic Resistance ◽  
Content Type ◽  
Class A ◽  
Resistance Transfer

ABSTRACT Burkholderia pseudomallei, the founding member of the B. pseudomallei complex (Bpc), is a biothreat agent and causes melioidosis, a disease whose treatment mainly relies on ceftazidime and meropenem. The concern is that B. pseudomallei could enhance its drug resistance repertoire by the acquisition of DNA from resistant near-neighbor species. Burkholderia ubonensis, a member of the B. cepacia complex (Bcc), is commonly coisolated from environments where B. pseudomallei is present. Unlike B. pseudomallei, in which significant primary carbapenem resistance is rare, it is not uncommon in B. ubonensis, but the underlying mechanisms are unknown. We established that carbapenem resistance in B. ubonensis is due to an inducible class A PenB β-lactamase, as has been shown for other Bcc bacteria. Inducibility is not sufficient for high-level resistance but also requires other determinants, such as a PenB that is more robust than that present in susceptible isolates, as well as other resistance factors. Curiously and diagnostic for the two complexes, both Bpc and Bcc bacteria contain distinct annotated PenA class A β-lactamases. However, the protein from Bcc bacteria is missing its essential active-site serine and, therefore, is not a β-lactamase. Regulated expression of a transcriptional penB′-lacZ (β-galactosidase) fusion in the B. pseudomallei surrogate B. thailandensis confirms that although Bpc bacteria lack an inducible β-lactamase, they contain the components required for responding to aberrant peptidoglycan synthesis resulting from β-lactam challenge. Understanding the diversity of antimicrobial resistance in Burkholderia species is informative about how the challenges arising from potential resistance transfer between them can be met. IMPORTANCE Burkholderia pseudomallei causes melioidosis, a tropical disease that is highly fatal if not properly treated. Our data show that, in contrast to B. pseudomallei, B. ubonensis β-lactam resistance is fundamentally different because intrinsic resistance is mediated by an inducible class A β-lactamase. This includes resistance to carbapenems. Our work demonstrates that studies with near-neighbor species are informative about the diversity of antimicrobial resistance in Burkholderia and can also provide clues about the potential of resistance transfer between bacteria inhabiting the same environment. Knowledge about potential adverse challenges resulting from the horizontal transfer of resistance genes between members of the two complexes enables the design of effective countermeasures.

scholarly journals New Auranofin Analogs with Antibacterial Properties against Burkholderia Clinical Isolates

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1443
Author(s):  
Dustin Maydaniuk ◽  
Bin Wu ◽  
Dang Truong ◽  
Sajani H. Liyanage ◽  
Andrew M. Hogan ◽  
...  
Keyword(s):  
Burkholderia Cepacia ◽  
Galleria Mellonella ◽  
Therapeutic Potential ◽  
Antibacterial Properties ◽  
Antimicrobial Properties ◽  
Clinical Isolates ◽  
Burkholderia Cepacia Complex ◽  
Model Organisms ◽  
Gram Positive Bacteria ◽  
High Concentrations

Bacteria of the genus Burkholderia include pathogenic Burkholderia mallei, Burkholderia pseudomallei and the Burkholderia cepacia complex (Bcc). These Gram-negative pathogens have intrinsic drug resistance, which makes treatment of infections difficult. Bcc affects individuals with cystic fibrosis (CF) and the species B. cenocepacia is associated with one of the worst clinical outcomes. Following the repurposing of auranofin as an antibacterial against Gram-positive bacteria, we previously synthetized auranofin analogs with activity against Gram-negatives. In this work, we show that two auranofin analogs, MS-40S and MS-40, have antibiotic activity against Burkholderia clinical isolates. The compounds are bactericidal against B. cenocepacia and kill stationary-phase cells and persisters without selecting for multistep resistance. Caenorhabditis elegans and Galleria mellonella tolerated high concentrations of MS-40S and MS-40, demonstrating that these compounds have low toxicity in these model organisms. In summary, we show that MS-40 and MS-40S have antimicrobial properties that warrant further investigations to determine their therapeutic potential against Burkholderia infections.

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