Integron occurrence is linked to reduced biocide susceptibility in multidrug resistantPseudomonas aeruginosa

Kadry, Azza M.; Serry, Fathy; El-Ganiny, Amira M.; El-Baz, Ahmed M.

doi:10.1080/09674845.2017.1278884

Cited by 29 publications

(21 citation statements)

References 28 publications

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“…MDR isolates represents a prominent health problem in Egypt due to several factors including misuse of antibiotics and biocides 30 . In the current study, 50 P. aeruginosa isolates were recovered from urine samples, all the isolates were MDR (100%), this MDR rate was higher than rates reported previously in Egypt which ranged from 34% – 56% 31 – 33 ; this may reflect higher resistance rate in case of urinary tract infections. Other global studies showed even lower MDR rates; 5.9% in Canada 34 , 19% in Germany 35 , 19.6 % in Malaysia 36 and 20.7% in Nepal 37 .…”

Section: Discussioncontrasting

confidence: 58%

Phenotypic and genotypic detection of antibiotic resistance of Pseudomonas aeruginosa isolated from urinary tract infections

Abbas¹,

El-Ganiny²,

Kamel³

2018

Afr H. Sci.

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BakgroundPseudomonas aeruginosa is a major nosocomial uropathogen. It can tolerate a wide variety of physical conditions and many antibiotics by different resistance mechanisms.ObjectivesThis study aimed to investigate the mechanisms of antibiotics resistance in uropathogenic P. aeruginosa clinical isolates.MethodsTwo hundred sixty six urine samples were collected from Zagazig University Hospitals, Zagazig, Egypt. P. aeruginosa isolates were identified using standard microbiological tests. The sensitivity to different antibiotics was determined by disc diffusion method. Anti-microbial resistance mechanisms were investigated using phenotypic methods and confirmed by PCR.ResultsFifty P. aeruginosa isolates were recovered. All isolates were MDR and were resistant to amoxicillin/clavulinic, sulphamethaxzole/trimethoprim, doxycycline and ceftazidime. Phenotypic detection of resistance mechanisms revealed that all strains have efflux mechanism, outer membrane porins, and AmpC β-lactamase; none of the strains showed ESBL activity and two of the imipenem resistant strains showed MβL activity. PCR analysis showed that all strains have MexAB-R, OprD and AmpC genes, 42 strains had PSE gene, while VEB and VIM genes were not detected.ConclusionThe resistance rates in P. aeruginosa were higher than global values; this resistance was attributed to several mechanisms. This high resistance is alarming and necessitates applying strict antibiotic prescription policies.

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Section: Discussioncontrasting

confidence: 58%

Phenotypic and genotypic detection of antibiotic resistance of Pseudomonas aeruginosa isolated from urinary tract infections

Abbas¹,

El-Ganiny²,

Kamel³

2018

Afr H. Sci.

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“…25,26 However, our results about the frequency of class 1 integrons among MDR P. aeruginosa isolates (63.4%) were comparable with a similar study carried out in Egypt (61.1%). 27 This difference may be due to the different policies and management of antibiotics for the treatment of infections in the world. Also, this rate was more varied in the southeast Asia from 38% to 95%, 3,[28][29][30][31][32] while 22% to 47% of the P. aeruginosa clinical isolates in European countries were contained the class 1 integrons between 2007 to 2013.…”

Section: Discussionmentioning

confidence: 99%

Distribution and Molecular Characterization of Resistance Gene Cassettes Containing Class 1 Integrons in Multi-Drug Resistant (MDR) Clinical Isolates of Pseudomonas aeruginosa

Ahmadian¹,

Haghshenas²,

Mirzaei³

et al. 2020

IDR

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The integrons, as the mobile exogenous elements, play a prominent role in the spreading of antimicrobial resistance genes from Pseudomonas aeruginosa clinical isolates to other bacteria. This study aimed to investigate the frequency of class 1 integrons andresistance gene cassettes carrying by them in clinical isolates as well as multidrug resistant P. aeruginosa. Materials and Methods: A total of 100 clinical isolates of P. aeruginosa were collected from 5 hospitals in Mazandaran province, north Iran. The antibiotic susceptibility pattern of the isolates was evaluated using the disk agar diffusion method. Genomic DNAs were extracted and then the presence of class 1 integrons was detected by the PCR test. All PCR products of the positive isolates were sequenced for the detection of resistance gene cassettes by the Sanger method. Results: Forty-one percent of the clinical isolates were multi-drug resistant. Also, 42% of the isolates were contained class 1 integron, and 61.9% of the integron positive isolates were detected as MDR. We detected 10 different gene cassettes sizing from 0.6 to 3.5 kb in the present study. The sequencing analysis of the internal variable regions of the class 1 integrons showed that the 0.75 kb gene cassette (aadB) was the most frequent resistance gene (54.76%) among all clinical isolates, as well as the MDR isolates. Other resistance genes detected in this study were included: aadA6-orfD (35.71%), aacA4-bla OXA-10 (21.42%), aadB-aacA4-bla OXA-10 (19.04%), bla OXA-10-aacA4-VIM1 (11.9%), aacA4-cat B10 (7.14%), aacA5-aadA1-cmlA5 (7.14%), bla OXA31-aadA2 (4.76%), and aac(3)-Ic-aac A5-cmlA5 (4.76%). To the best of our knowledge, bla OXA-10-aacA4-VIM1 cassette array is detected for the first time in this study. Conclusion: The treatment of infections caused by P. aeruginosa in this region of Iran is a major problem due to the high prevalence of class 1 integrons. It seems that the high prescription of beta-lactams and aminoglycosides for the treatment of these infections may be replaced by other combination therapy stewardships.

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“…This, alongside the broad range of substrates (QAC compounds, disinfectants, antibiotics, etc.) that SMRs can extrude and their increasing prevalence on plasmids and integrons in clinical and multidrug-resistant strains of bacteria (13,(27)(28)(29)(30)(31)(32)(33)(34)(35), marks these proteins as important therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

“…The primary substrates of SMRs include quaternary ammonium compounds (QACs), a broad category that includes the fluorescent toxic molecule ethidium bromide (EtBr) and many biocides, including cetylpyridinium chloride (CPϩ), cetyltrimethylammonium bromide (CTAB), and benzalkonium chloride (BZK); the latter is a commonly used hospital disinfectant (12). Of particular relevance to the present study is the strong correlation observed between the presence of genes encoding SMR proteins in P. aeruginosa clinical isolates and increased resistance to common disinfectants, including benzalkonium chloride (13).…”

mentioning

confidence: 91%

Peptide-Based Efflux Pump Inhibitors of the Small Multidrug Resistance Protein from Pseudomonas aeruginosa

Mitchell

Stone

Deber

2019

Antimicrob Agents Chemother

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Bacteria have acquired multiple mechanisms to evade the lethal effects of current therapeutics, hindering treatment of bacterial infections, such as those caused by the pathogen Pseudomonas aeruginosa, which is responsible for nosocomial and cystic fibrosis lung infections. One resistance mechanism involves membrane-embedded multidrug efflux pumps that can effectively extrude an array of substrates, including common antibiotics, dyes, and biocides. Among these is a small multidrug resistance (SMR) efflux protein, consisting of four transmembrane (TM) helices, that functions as an antiparallel dimer. TM helices 1 to 3 (TM1 to TM3) comprise the substrate binding pocket, while TM4 contains a GG7 heptad sequence motif that mediates the SMR TM4-TM4 dimerization. In the present work, we synthesized a series of peptides containing the residues centered on the TM4-TM4 binding interface found in the P. aeruginosa SMR (PAsmr), typified by Ac-Ala-(Sar)3-LLGIGLIIAGVLV-KKK-NH2 (helix-helix interaction residues are underlined). Here, the acetylated N-terminal sarcosine (N-methyl-Gly) tag [Ac-Ala-(Sar)3] promotes membrane penetration, while the C-terminal Lys tag promotes selectivity for the negatively charged bacterial membranes. This peptide was observed to competitively disrupt PAsmr-mediated efflux, as measured by efflux inhibition of the fluorescent dye ethidium bromide, while having no effect on cell membrane integrity. Alternatively, a corresponding peptide in which the TM4 binding motif is scrambled was inactive in this assay. In addition, when Escherichia coli cells expressing PAsmr were combined with sublethal concentrations of several biocides, growth was significantly inhibited when peptide was added, notably, by up to 95% with the disinfectant benzylalkonium chloride. These results demonstrate promise for an efflux pump inhibitor to address the increasing threat of antibiotic-resistant bacteria.

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Integron occurrence is linked to reduced biocide susceptibility in multidrug resistantPseudomonas aeruginosa

Cited by 29 publications

References 28 publications

Phenotypic and genotypic detection of antibiotic resistance of Pseudomonas aeruginosa isolated from urinary tract infections

Phenotypic and genotypic detection of antibiotic resistance of Pseudomonas aeruginosa isolated from urinary tract infections

<p>Distribution and Molecular Characterization of Resistance Gene Cassettes Containing Class 1 Integrons in Multi-Drug Resistant (MDR) Clinical Isolates of <em>Pseudomonas aeruginosa</em></p>

Peptide-Based Efflux Pump Inhibitors of the Small Multidrug Resistance Protein from Pseudomonas aeruginosa

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