Polymyxin B Heteroresistance and Adaptive Resistance in Multidrug- and Extremely Drug-Resistant Acinetobacter baumannii

Genteluci, Gabrielle Limeira; Souza, Paula Araújo de; Gomes, Daniela Betzler Cardoso; Sousa, Verônica Santos; Souza, Maria José de; Abib, José Roberto Lannes; Castro, Edna Aparecida Barbosa de; Rangel, Karyne; Bôas, Maria Helena Simões Villas

doi:10.1007/s00284-020-02064-6

Cited by 14 publications

(9 citation statements)

References 38 publications

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“…As the results shown, Polymixins (PMb ) are the most effective antimicrobial agents in agreement with previous reports .Although the e cacy of Polymixins have declared in studies ,their prescription are con ned because of its neurotoxic or nephrotoxic side effects (28,29).Acquisition of foreign genetic elements such as integrons leads to emerge the resistant phenotypes. The spread of these mobile elements between species causes the extension of resistance in health-care settings.…”

Section: Discussionsupporting

confidence: 85%

Antimicrobial susceptibility profiles, presence of integrons and associated cassette genes among Acinetobacter baumannii isolates from Southern part of Iran, Shiraz

Khoramrooz

Eslami

Motamedifar

et al. 2021

Preprint

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Background Acinetobacter baumannii is a global concern to cause the health-care-associated infections, due to multidrug resistance against available commercially antimicrobial agents. Regarding this, the present study was conducted to determine the antimicrobial susceptibility of A.baumannii isolates from clinical specimens in Shiraz, and explore the possible relationship of susceptibility patterns with the presence of integrons and related gene cassettes. Methods A.baumannii isolates were collected, and their susceptibility to various antibiotics was tested using Kirby-Bauer disk diffusion method. Also, molecular analyses were performed to detect the presence of OXA-51 like gene, class I, II and III integrons, and associated gene cassettes. Results Majority of isolates demonstrated resistance to imipenem(99.4%),piperacilin(98.2%),gentamycin (98.2%) meropenem (97.7%)ceftazidime(95.4%)amikacin(95.4%) and trimethoprim-sulfamethoxazole (90.8%). All strains showed multidrug-resistance to most of the tested antibiotics. The distribution analysis of integrons genes showed that 90.2%, 72.4% and 12.1% of isolates carried the intI 1, intI2 and intI3 genes, respectively. Moreover, two types of prevalent gene cassettes including aad and dfr were detected in Class 1 integron-carrying strains. Conclusions The current study showed the high prevalence of A.baumannii isolates harboring integrons in our investigated medical center, which may propel distribution of multidrug resistance event. The different types of gene cassette arrays in the present study spotlight the remarkable role of geographical issues in MDR isolates dissemination. This subject could attribute to choose appropriate therapeutic interventions in different areas. Obtained data highlighted the necessity for continuous surveillance to prevent distribution of multidrug resistance among A.baumannii strains in Iran.

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Section: Discussionsupporting

confidence: 85%

Antimicrobial susceptibility profiles, presence of integrons and associated cassette genes among Acinetobacter baumannii isolates from Southern part of Iran, Shiraz

Khoramrooz

Eslami

Motamedifar

et al. 2021

Preprint

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“…In addition, formation of biofilm drastically enhances the bacterial resistance to antibiotics [7]. Polymyxin B and colistin (polymyxin E) are cyclic polypeptide antibiotics that are used as the last-resort treatment option against serious infections caused by Gram-negative bacteria, including P. aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii [7][8][9][10]. Polymyxin B and colistin are very similar in their structures, both consisting of a cyclic heptapeptide, a linear tripeptide, and a fatty acid chain [11].…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel phoP-phoQ Regulated Genes that Contribute to Polymyxin B Tolerance in Pseudomonas aeruginosa

et al. 2021

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Polymyxin B and E (colistin) are the last resorts to treat multidrug-resistant Gram-negative pathogens. Pseudomonas aeruginosa is intrinsically resistant to a variety of antibiotics. The PhoP-PhoQ two-component regulatory system contributes to the resistance to polymyxins by regulating an arnBCADTEF-pmrE operon that encodes lipopolysaccharide modification enzymes. To identify additional PhoP-regulated genes that contribute to the tolerance to polymyxin B, we performed a chromatin immunoprecipitation sequencing (ChIP-Seq) assay and found novel PhoP binding sites on the chromosome. We further verified that PhoP directly controls the expression of PA14_46900, PA14_50740 and PA14_52340, and the operons of PA14_11970-PA14_11960 and PA14_52350-PA14_52370. Our results demonstrated that mutation of PA14_46900 increased the bacterial binding and susceptibility to polymyxin B. Meanwhile, mutation of PA14_11960 (papP), PA14_11970 (mpl), PA14_50740 (slyB), PA14_52350 (ppgS), and PA14_52370 (ppgH) reduced the bacterial survival rates and increased ethidium bromide influx under polymyxin B or Sodium dodecyl sulfate (SDS) treatment, indicating roles of these genes in maintaining membrane integrity in response to the stresses. By 1-N-phenylnaphthylamine (NPN) and propidium iodide (PI) staining assay, we found that papP and slyB are involved in maintaining outer membrane integrity, and mpl and ppgS-ppgH are involved in maintaining inner membrane integrity. Overall, our results reveal novel PhoP-PhoQ regulated genes that contribute to polymyxin B tolerance.

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“…The mechanisms of resistance to PMB are associated with the two-component systems PhoP/PhoQ and PmrA/PmrB, while those to TGC are associated with the overexpression of AcrAB-TolC and OqxAB efflux pumps. In addition, the ongoing discovery of heteroresistance to PMB and TGC is also of concern ( 17 , 18 ).…”

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confidence: 99%

Combined effect of Polymyxin B and Tigecycline to overcome Heteroresistance in Carbapenem-Resistant Klebsiella pneumoniae

et al. 2021

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Polymyxin B Heteroresistance and Adaptive Resistance in Multidrug- and Extremely Drug-Resistant Acinetobacter baumannii

Cited by 14 publications

References 38 publications

Antimicrobial susceptibility profiles, presence of integrons and associated cassette genes among Acinetobacter baumannii isolates from Southern part of Iran, Shiraz

Antimicrobial susceptibility profiles, presence of integrons and associated cassette genes among Acinetobacter baumannii isolates from Southern part of Iran, Shiraz

Identification of Novel phoP-phoQ Regulated Genes that Contribute to Polymyxin B Tolerance in Pseudomonas aeruginosa

Combined effect of Polymyxin B and Tigecycline to overcome Heteroresistance in Carbapenem-Resistant Klebsiella pneumoniae

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