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

Burkholderia cepacia complex (Bcc) and Burkholderia pseudomallei complex (Bpc) species include pathogens that are typically multidrug resistant. Dominant intrinsic and acquired multidrug resistance mechanisms are efflux mediated by pumps of the resistance nodulation cell division (RND) family. From comparative bioinformatic and, in many instances, functional studies we infer that RND pump-based resistance mechanisms are conserved in Burkholderia . We propose to use these findings as a foundation for adoption of a uniform RND efflux pump nomenclature.

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Potential of metabolomics to reveal Burkholderia cepacia complex pathogenesis and antibiotic resistance

Frontiers in Microbiology ◽

10.3389/fmicb.2015.00668 ◽

2015 ◽

Vol 6 ◽

Cited By ~ 9

Author(s):

Nusrat S. Shommu ◽

Hans J. Vogel ◽

Douglas G. Storey

Keyword(s):

Antibiotic Resistance ◽

Burkholderia Cepacia ◽

Burkholderia Cepacia Complex

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80 Investigation of the potential mechanisms of antibiotic resistance in the cystic fibrosis pathogen, Burkholderia cepacia complex

Journal of Cystic Fibrosis ◽

10.1016/s1569-1993(12)60250-1 ◽

2012 ◽

Vol 11 ◽

pp. S77

Author(s):

S. Kennedy ◽

K. Carroll ◽

E. Caraher

Keyword(s):

Cystic Fibrosis ◽

Antibiotic Resistance ◽

Burkholderia Cepacia ◽

Burkholderia Cepacia Complex

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Two resistance nodulation division-family efflux pumps inChromobacteriumspecies and their role in antibiotic resistance and tolerance

10.1101/562140 ◽

2019 ◽

Author(s):

Saida Benomar ◽

Kara C Evans ◽

Robert L Unckless ◽

Josephine R Chandler

Keyword(s):

Antibiotic Resistance ◽

Efflux Pump ◽

Bacterial Species ◽

Efflux Pumps ◽

Resistance Mechanisms ◽

Antibiotic Resistant ◽

Burkholderia Thailandensis ◽

New Information ◽

Resistance Nodulation Division ◽

Culture Growth

ABSTRACTVery little is known of the antibiotic resistance mechanisms of members of theChromobacteriumgenus. In previous studies ofChromobacterium subtsugae(formerlyC. violaceum) strain CV017, we identified a resistance nodulation division (RND)-family efflux pump (CdeAB-OprM). Here, we show thecdeAB-oprMgenes are widely distributed in members of theChromobacteriumgenus. We use antimicrobial susceptibility testing with a CV017cdeAB-oprMmutant to show the products of these genes confers resistance to a variety of antibiotics including ciprofloxacin, a clinically important antibiotic. We also identified a related RND-family pump,cseAB-oprN, in the genome of CV017 and otherC. subtsugaespecies, that is not present in other members of theChromobacteriumgenus. We demonstrate that CdeAB-OprM and CseAB-OprN are both transcriptionally induced in CV017 cells treated with sub-lethal antibiotic concentrations and they are important for induction of tolerance to different antibiotics. While CdeAB-OprM has a broad antibiotic specificity, the CseAB-OprN system is highly specific for a ribosome-targeting antibiotic produced by the saprophytic bacteriumBurkholderia thailandensis,bactobolin. Finally, we use a previously developedB. thailandensis-C. subtsugaeCV017 co-culture model to demonstrate that adding sub-lethal bactobolin at the beginning of co-culture growth increases the ability of CV017 to compete withB. thailandensisin a manner that is dependent on the CseAB-OprN system. Our results provide new information on the antibiotic resistance mechanisms ofChromobacteriumspecies and highlight the importance of efflux pumps during competition with other bacterial species.IMPORTANCEThis study describes two closely related efflux pumps in members of theChromobacteriumgenus, which includes opportunistic but often-fatal pathogens and species with highly versatile metabolic capabilities. Efflux pumps remove antibiotics from the cell and are important for antibiotic resistance. One of these pumps is broadly distributed in theChromobacteriumgenus and increases resistance to clinically relevant antibiotics. The other efflux pump is present only inChromobacterium subtsugaeand is highly specific for bactobolin, an antibiotic produced by the soil saprophyteBurkholderia thailandensis. We demonstrate these pumps can be activated to increase resistance by their antibiotic substrates, and that this activation is important forC. subtsugaeto survive in a laboratory competition experiment withB. thailandensis.These results have implications for managing antibiotic-resistantChromobacteriuminfections, bioengineering ofChromobacteriumspecies, and for understanding the evolution of efflux pumps.

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Draft Genome Sequence of Flavobacterium sp. Strain TAB 87, Able To Inhibit the Growth of Cystic Fibrosis Bacterial Pathogens Belonging to the Burkholderia cepacia Complex

Genome Announcements ◽

10.1128/genomea.00410-16 ◽

2016 ◽

Vol 4 (3) ◽

Cited By ~ 1

Author(s):

Luana Presta ◽

Ilaria Inzucchi ◽

Emanuele Bosi ◽

Marco Fondi ◽

Elena Perrin ◽

...

Keyword(s):

Cystic Fibrosis ◽

Antibiotic Resistance ◽

Comparative Genomics ◽

Bioactive Compounds ◽

Genome Sequence ◽

Burkholderia Cepacia ◽

Draft Genome ◽

Burkholderia Cepacia Complex ◽

Draft Genome Sequence ◽

Antarctic Seawater

We report here the draft genome sequence of the Flavobacterium sp. TAB 87 strain, isolated from Antarctic seawater during a summer campaign near the French Antarctic station Dumont d’Urville (60°40′S, 40°01′E). It will allow for comparative genomics and the fulfillment of both fundamental and application-oriented investigations. It allowed the recognition of genes associated with the production of bioactive compounds and antibiotic resistance.

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PA3225 Is a Transcriptional Repressor of Antibiotic Resistance Mechanisms in Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02114-16 ◽

2017 ◽

Vol 61 (8) ◽

Cited By ~ 5

Author(s):

Clayton W. Hall ◽

Li Zhang ◽

Thien-Fah Mah

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Efflux Pump ◽

Regulatory Region ◽

Resistance Mechanisms ◽

Wild Type ◽

Type Vi Secretion System ◽

Planktonic Cells ◽

Content Type ◽

Dependent Protein

ABSTRACT The tssABC1 locus is part of the Hcp secretion island I (HSI-I) type VI secretion system (T6SS) in Pseudomonas aeruginosa. Previous work implicated the tssC1 gene in P. aeruginosa biofilm-specific antibiotic resistance, and tssC1 is preferentially expressed in biofilms compared to planktonic cells. Using a DNA-dependent protein pulldown approach, we discovered that PA3225, an uncharacterized LysR-type transcriptional regulator, specifically bound to the tssABC1 upstream regulatory region. The deletion of PA3225 led to a 2-fold decrease in tssA1 expression levels in planktonic cells compared to the wild type, and tssA1 expression was slightly reduced in ΔPA3225 biofilms compared to wild-type biofilms. Intriguingly, further investigations revealed that the ΔPA3225 mutant was less susceptible to multiple, structurally unrelated antibiotics with various mechanisms of action when grown planktonically. The ΔPA3225 mutant was additionally more resistant to ciprofloxacin when grown in a biofilm. The decreased antibiotic susceptibility of the ΔPA3225 strain was linked to the transcriptional upregulation of the MexAB-OprM efflux pump. By using transcriptome sequencing (RNA-seq), other PA3225-regulated genes were identified, and the products of these genes, such as the putative ABC transporter PA3228, may also contribute to antibiotic resistance.

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Pleiotropy complicates a trade-off between phage resistance and antibiotic resistance

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1919888117 ◽

2020 ◽

Vol 117 (21) ◽

pp. 11207-11216 ◽

Cited By ~ 14

Author(s):

Alita R. Burmeister ◽

Abigail Fortier ◽

Carli Roush ◽

Adam J. Lessing ◽

Rose G. Bender ◽

...

Keyword(s):

Antibiotic Resistance ◽

Molecular Mechanisms ◽

Efflux Pump ◽

Resistance Mechanisms ◽

Phage Resistance ◽

Resistance Mutations ◽

Trade Off ◽

Trade Offs ◽

Evolutionary Context ◽

Structural Barrier

Bacteria frequently encounter selection by both antibiotics and lytic bacteriophages. However, the evolutionary interactions between antibiotics and phages remain unclear, in particular, whether and when phages can drive evolutionary trade-offs with antibiotic resistance. Here, we describeEscherichia coliphage U136B, showing it relies on two host factors involved in different antibiotic resistance mechanisms: 1) the efflux pump protein TolC and 2) the structural barrier molecule lipopolysaccharide (LPS). Since TolC and LPS contribute to antibiotic resistance, phage U136B should select for their loss or modification, thereby driving a trade-off between phage resistance and either of the antibiotic resistance mechanisms. To test this hypothesis, we used fluctuation experiments and experimental evolution to obtain phage-resistant mutants. Using these mutants, we compared the accessibility of specific mutations (revealed in the fluctuation experiments) to their actual success during ecological competition and coevolution (revealed in the evolution experiments). BothtolCand LPS-related mutants arise readily during fluctuation assays, withtolCmutations becoming more common during the evolution experiments. In support of the trade-off hypothesis, phage resistance viatolCmutations occurs with a corresponding reduction in antibiotic resistance in many cases. However, contrary to the hypothesis, some phage resistance mutations pleiotropically confer increased antibiotic resistance. We discuss the molecular mechanisms underlying this surprising pleiotropic result, consideration for applied phage biology, and the importance of ecology in evolution of phage resistance. We envision that phages may be useful for the reversal of antibiotic resistance, but such applications will need to account for unexpected pleiotropy and evolutionary context.

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Antibiotic resistance trends and mechanisms in the foodborne pathogen,Campylobacter

Animal Health Research Reviews ◽

10.1017/s1466252317000135 ◽

2017 ◽

Vol 18 (2) ◽

pp. 87-98 ◽

Cited By ~ 22

Author(s):

Yizhi Tang ◽

Liangxing Fang ◽

Changyun Xu ◽

Qijing Zhang

Keyword(s):

Antibiotic Resistance ◽

Efflux Pump ◽

Foodborne Pathogen ◽

Resistance Mechanisms ◽

World Health ◽

Antibiotic Resistant ◽

Innovative Strategies ◽

Control And Prevention ◽

Antibiotic Selection Pressure ◽

Health Organization

AbstractCampylobacteris a major foodborne pathogen and is commonly present in food producing animals. This pathogenic organism is highly adaptable and has become increasingly resistant to various antibiotics. Recently, both the Centers for Disease Control and Prevention and the World Health Organization have designated antibiotic-resistantCampylobacteras a serious threat to public health. For the past decade, multiple mechanisms conferring resistance to clinically important antibiotics have been described inCampylobacter, and new resistance mechanisms constantly emerge in the pathogen. Some of the recent examples include theerm(B)gene conferring macrolide resistance, thecfr(C)genes mediating resistance to florfenicol and other antimicrobials, and a functionally enhanced variant of the multidrug resistance efflux pump, CmeABC. The continued emergence of new resistance mechanisms illustrates the extraordinary adaptability ofCampylobacterto antibiotic selection pressure and demonstrate the need for innovative strategies to control antibiotic-resistantCampylobacter. In this review, we will briefly summarize the trends of antibiotic resistance inCampylobacterand discuss the mechanisms of resistance to antibiotics used for animal production and important for clinical therapy in humans. A special emphasis will be given to the newly discovered antibiotic resistance.

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Intensity and Mechanisms of Fluoroquinolone Resistance within theH30 andH30Rx Subclones of Escherichia coli Sequence Type 131 Compared with Other Fluoroquinolone-Resistant E. coli

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00673-15 ◽

2015 ◽

Vol 59 (8) ◽

pp. 4471-4480 ◽

Cited By ~ 37

Author(s):

James R. Johnson ◽

Brian Johnston ◽

Michael A. Kuskowski ◽

Evgeni V. Sokurenko ◽

Veronika Tchesnokova

Keyword(s):

Escherichia Coli ◽

Efflux Pump ◽

Resistance Mechanisms ◽

Sequence Type ◽

Fluoroquinolone Resistance ◽

Solvent Tolerance ◽

Organic Solvent Tolerance ◽

Content Type ◽

E Coli ◽

Pump Activity

ABSTRACTThe recent expansion of theH30 subclone ofEscherichia colisequence type 131 (ST131) and its CTX-M-15-associatedH30Rx subset remains unexplained. Although ST131H30 typically exhibits fluoroquinolone resistance, so do multiple otherE. colilineages that have not expanded similarly. To determine whetherH30 isolates have more intense fluoroquinolone resistance than other fluoroquinolone-resistantE. coliisolates and to identify possible mechanisms, we determined the MICs for four fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, and norfloxacin) among 89 well-characterized, genetically diverse fluoroquinolone-resistantE. coliisolates (48 non-H30 and 41H30 [23H30Rx and 18H30 non-Rx]). We compared the MICs with theH30 andH30Rx status, the presence/number of nonsynonymous mutations ingyrA,parC, andparE, the presence ofaac(6′)-1b-cr(an aminoglycoside/fluoroquinolone agent-modifying enzyme), and the efflux pump activity (measured as organic solvent tolerance [OST]). Among 1,518 recentE. coliclinical isolates, ST131H30 predominated clonally, both overall and among the fluoroquinolone-resistant isolates. Among the 89 study isolates, compared with non-H30 isolates,H30 isolates exhibited categorically higher MICs for all four fluoroquinolone agents, higher absolute ciprofloxacin and norfloxacin MICs, more nonsynonymous mutations ingyrA,parC, andparE(specificallygyrAD87N,parCE84V, andparEI529L), and a numerically higher prevalence of (H30Rx-associated)aac(6′)-1b-crbut lower OST scores. All putative resistance mechanisms were significantly associated with the MICs [foraac(6′)-1b-cr: ciprofloxacin and norfloxacin only].parCD87N corresponded with ST131H30 andparEI529L with ST131 generally. Thus, more intense fluoroquinolone resistance may provide ST131H30, especiallyH30Rx [ifaac(6′)-1b-crpositive], with subtle fitness advantages over other fluoroquinolone-resistantE. colistrains. This urges both parsimonious fluoroquinolone use and a search for other fitness-enhancing traits within ST131H30.

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