Gene expression analysis of the SdeAB multidrug efflux pump in antibiotic-resistant clinical isolates of Serratia marcescens

Dalvi, SD; Worobec, EA

doi:10.4103/0255-0857.99491

Cited by 10 publications

(7 citation statements)

References 14 publications

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“…Although we did not analyze the genes Sde A e Sde X, the genes Sde B and Sde X were present in all strains and the gene Has F was also found in most strains. Drug extrusion by efflux pumps as Sde AB- Has F comprises one of the main mechanisms for fluoroquinolones antibiotic resistance ( Dalvi and Worobec, 2012 ). Additionally, Hornsey et al (2010) has shown the intrinsic activity of the Sde XY- Ha sF efflux pump is responsible for the lower susceptibility to ciprofloxacin.…”

Section: Discussionmentioning

confidence: 99%

Characterization of KPC-Producing Serratia marcescens in an Intensive Care Unit of a Brazilian Tertiary Hospital

et al. 2020

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Serratia marcescens has emerged as an important opportunistic pathogen responsible for nosocomial and severe infections. Here, we determined phenotypic and molecular characteristics of 54 S. marcescens isolates obtained from patient samples from intensive-care-unit (ICU) and neonatal intensive-care-unit (NIUC) of a Brazilian tertiary hospital. All isolates were resistant to beta-lactam group antibiotics, and 92.6% (50/54) were not susceptible to tigecycline. Furthermore, 96.3% showed intrinsic resistance to polymyxin E (colistin), a last-resort antibiotic for the treatment of infections caused by MDR (multidrug-resistant) Gram-negative bacteria. In contrast, high susceptibility to other antibiotics such as fluoroquinolones (81.5%), and to aminoglycosides (as gentamicin 81.5%, and amikacin 85.2%) was found. Of all isolates, 24.1% were classified as MDR. The presence of resistance and virulence genes were examined by PCR and sequencing. All isolates carried KPC-carbapenemase (bla KPC) and extended spectrum beta-lactamase bla TEM genes, 14.8% carried bla OXA−1 , and 16.7% carried bla CTX−M−1group genes, suggesting that bacterial resistance to β-lactam antibiotics found may be associated with these genes. The genes SdeB/HasF and SdeY/HasF that are associated with efflux pump mediated drug extrusion to fluoroquinolones and tigecycline, respectively, were found in 88.9%. The aac(6)-Ib-cr variant gene that can simultaneously induce resistance to aminoglycoside and fluoroquinolone was present in 24.1% of the isolates. Notably, the virulence genes to (i) pore-forming toxin (ShlA); (ii) phospholipase with hemolytic and cytolytic activities (PhlA); (iii) flagellar transcriptional regulator (FlhD); and (iv) positive regulator of prodigiosin and serratamolide production (PigP) were present in 98.2%. The genetic relationship among the isolates determined by ERIC-PCR demonstrated that the vast majority of isolates were grouped in a single cluster with 86.4% genetic similarity. In addition, many isolates showed 100% genetic similarity to each other, suggesting that the S. marcescens that circulate in this ICU are closely related. Our results suggest that the antimicrobial resistance to many drugs

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Section: Discussionmentioning

confidence: 99%

Characterization of KPC-Producing Serratia marcescens in an Intensive Care Unit of a Brazilian Tertiary Hospital

et al. 2020

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“…SdeY, however, has a sequence 84% identical to that of E. coli AcrB and should more properly be called AcrB. Thus, at present, the relative importance of AcrB and SdeB in fluoroquinolone efflux remains unclear, and the expression levels of sdeB in clinical isolates had no clear correlation with their fluoroquinolone resistance levels (325). An MFS pump (SmfY), an SMR pump (SsmE), and an ABC pump (SmdAB) increased the MICs of several drugs when expressed from a plasmid in E. coli (16).…”

Section: Serratia Marcescensmentioning

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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“…In S. marcescens , efflux pumps are currently not fully characterized. To date, six out of eight putative S. marcescens RND efflux pumps have been linked with multidrug resistance ( 13 – 17 ). In addition, the SMR-type pump SsmE and the MFS-type pump SmfY were shown to be involved in protection of S. marcescens from fluoroquinolones ( 18 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

The ABC-Type Efflux Pump MacAB Is Involved in Protection of Serratia marcescens against Aminoglycoside Antibiotics, Polymyxins, and Oxidative Stress

Shirshikova

Sierra-Bakhshi

Kamaletdinova

et al. 2021

mSphere

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Serratia marcescens is an emerging pathogen with increasing clinical importance due to its intrinsic resistance to several classes of antibiotics. The chromosomally encoded drug efflux pumps contribute to antibiotic resistance and represent a major challenge for the treatment of bacterial infections. The ABC-type efflux pump MacAB was previously linked to macrolide resistance in Escherichia coli and Salmonella enterica serovar Typhimurium. The role of the MacAB homolog in antibiotic resistance of S. marcescens is currently unknown. We found that an S. marcescens mutant lacking the MacAB pump did not show increased sensitivity to the macrolide antibiotic erythromycin but was significantly more sensitive to aminoglycoside antibiotics and polymyxins. We also showed that, in addition to its role in drug efflux, the MacAB efflux pump is required for swimming motility and biofilm formation. We propose that the motility defect of the ΔmacAB mutant is due, at least in part, to the loss of functional flagella on the bacterial surface. Furthermore, we found that the promoter of the MacAB efflux pump was active during the initial hours of growth in laboratory medium and that its activity was further elevated in the presence of hydrogen peroxide. Finally, we demonstrate a complete loss of ΔmacAB mutant viability in the presence of peroxide, which is fully restored by complementation. Thus, the S. marcescens MacAB efflux pump is essential for survival during oxidative stress and is involved in protection from polymyxins and aminoglycoside antibiotics. IMPORTANCE The opportunistic pathogen Serratia marcescens can cause urinary tract infections, respiratory infections, meningitis, and sepsis in immunocompromised individuals. These infections are challenging to treat due to the intrinsic resistance of S. marcescens to an extensive array of antibiotics. Efflux pumps play a crucial role in protection of bacteria from antimicrobials. The MacAB efflux pump, previously linked to efflux of macrolides in Escherichia coli and protection from oxidative stress in Salmonella enterica serovar Typhimurium, is not characterized in S. marcescens. We show the role of the MacAB efflux pump in S. marcescens protection from aminoglycoside antibiotics and polymyxins, modulation of bacterial motility, and biofilm formation, and we illustrate the essential role for this pump in bacterial survival during oxidative stress. Our findings make the MacAB efflux pump an attractive target for inhibition to gain control over S. marcescens infections.

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Gene expression analysis of the SdeAB multidrug efflux pump in antibiotic-resistant clinical isolates of Serratia marcescens

Cited by 10 publications

References 14 publications

Characterization of KPC-Producing Serratia marcescens in an Intensive Care Unit of a Brazilian Tertiary Hospital

Characterization of KPC-Producing Serratia marcescens in an Intensive Care Unit of a Brazilian Tertiary Hospital

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

The ABC-Type Efflux Pump MacAB Is Involved in Protection of Serratia marcescens against Aminoglycoside Antibiotics, Polymyxins, and Oxidative Stress

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