scholarly journals Comparative analysis of carbapenemases, RND family efflux pumps and biofilm formation potential among Acinetobacter baumannii strains with different carbapenem susceptibility

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yanpeng Zhang ◽  
Bing Fan ◽  
Yong Luo ◽  
Zhiyuan Tao ◽  
Yongbo Nie ◽  
...  
Keyword(s):  
Cell Division ◽  
Comparative Analysis ◽  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Carbapenem Resistance ◽  
Efflux Pumps ◽  
Relative Expression ◽  
Formation Potential ◽  
Tertiary Hospitals

Abstract Aim This study has conducted a comparative analysis of common carbapenemases harboring, the expression of resistance-nodulation-cell division (RND) family efflux pumps, and biofilm formation potential associated with carbapenem resistance among Acinetobacter baumannii (A. baumannii) strains with different carbapenem susceptibility. Methods: A total of 90 isolates of A. baumannii from two tertiary hospitals of China were identified and grouped as carbapenem susceptible A. baumannii (CSAB) strains and carbapenem non-susceptible A. baumannii (CnSAB) strains based on the susceptibility to imipenem. Harboring of carbapenemase genes, relative expression of RND family efflux pumps and biofilm formation potential were compared between the two groups. Result: Among these strains, 12 (13.3 %) strains were divided into the CSAB group, and 78 (86.7 %) strains into the CnSAB group. Compared with CSAB strains, CnSAB strains increased distribution of blaOXA−23 (p < 0.001) and ISAba1/blaOXA−51−like (p = 0.034) carbapenemase genes, and a 6.1-fold relative expression of adeB (p = 0.002), while CSAB strains led to biofilm formation by 1.3-fold than CnSAB strains (p = 0.021). Conclusions Clinically, harboring more blaOXA−23−like and ISAba1/blaOXA−51−like complex genes and overproduction of adeABC are relevant with carbapenem resistance, while carbapenem susceptible strains might survive the stress of antibiotic through their ability of higher biofilm formation.

scholarly journals Diversity of mutations in regulatory genes of resistance-nodulation-cell division efflux pumps in association with tigecycline resistance in Acinetobacter baumannii

2018 ◽  
Vol 73 (6) ◽  
pp. 1501-1508 ◽  
Author(s):  
Stefanie Gerson ◽  
Jennifer Nowak ◽  
Esther Zander ◽  
Julia Ertel ◽  
Yurong Wen ◽  
...  
Keyword(s):  
Cell Division ◽  
Acinetobacter Baumannii ◽  
Efflux Pumps ◽  
Regulatory Genes

scholarly journals Characteristics and diversity of mutations in regulatory genes of resistance-nodulation-cell division efflux pumps in association with drug-resistant clinical isolates of Acinetobacter baumannii

2020 ◽  
Author(s):  
Bahare Salehi ◽  
Zohreh Ghalavand ◽  
Abbas Yadegar ◽  
Gita Eslami
Keyword(s):  
Cell Division ◽  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Regulatory Genes ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Broth Microdilution Method ◽  
Rnd Efflux Pumps ◽  
Multiple Antibiotics

Abstract Background: This study aimed to characterize the regulation and expression of three putative resistance-nodulation-cell division (RND)-type efflux systems and their contribution to multidrug efflux in clinical isolates of Acinetobacter baumannii. Methods: Antimicrobial susceptibility testing (AST) of 95 A. baumannii isolates was determined by Kirby-Bauer disk diffusion for 18 antibiotics and minimum inhibitory concentration (MIC) of colistin was determined by broth microdilution method. Moreover, MIC of five classes of antibiotics was assessed using E-test strips in the presence and absence of phenylalanine-arginine beta-naphthylamide (PAβN). Regulatory genes of RND efflux pumps (AdeRS, AdeL, AdeN and BaeSR) were subjected to sequencing. The relative expression of adeB. adeG and adeJ genes was determined by quantitative real-time PCR (RT-PCR).Results: Overall, majority of isolates (93%) were extensively drug-resistant (XDR). In the phenotypic assay, efflux pump activity was observed in 40% of isolates against multiple antibiotics mainly tigecycline, but not to imipenem. Several amino acid substitutions were detected in the regulatory genes; except in AdeN. Of note, G186V in AdeS were found to be associated with overexpression of their relative efflux pumps. No insertion sequences (ISs) were detected. Conclusions: Our findings outline the role of RND efflux pumps in resistance of A. baumannii against multiple antibiotics particularly tigecycline, and point out importance of a variety of single mutations in the corresponding regulatory systems. Even though it has been concluded that multidrug resistance occurs as a result of a complex sets of different resistant mechanisms.

scholarly journals Characteristics and diversity of mutations in regulatory genes of resistance-nodulation-cell division efflux pumps in association with drug-resistant clinical isolates of Acinetobacter baumannii

2020 ◽  
Author(s):  
Bahare Salehi ◽  
Zohreh Ghalavand ◽  
Abbas Yadegar ◽  
Gita Eslami
Keyword(s):  
Cell Division ◽  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Regulatory Genes ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Broth Microdilution Method ◽  
Rnd Efflux Pumps ◽  
Multiple Antibiotics

Abstract Background: This study aimed to characterize the regulation and expression of three putative resistance-nodulation-cell division (RND)-type efflux systems and their contribution to multidrug efflux in clinical isolates of Acinetobacter baumannii.Methods: Antimicrobial susceptibility testing (AST) of 95 A. baumannii isolates was determined by Kirby-Bauer disk diffusion for 18 antibiotics and minimum inhibitory concentration (MIC) of colistin was determined by broth microdilution method. Moreover, MIC of five classes of antibiotics was assessed using E-test strips in the presence and absence of phenylalanine-arginine beta-naphthylamide (PAβN). Regulatory genes of RND efflux pumps (AdeRS, AdeL, AdeN and BaeSR) were subjected to sequencing. The relative expression of adeB. adeG and adeJ genes was determined by quantitative real-time PCR (RT-PCR).Results: Overall, majority of isolates (93%) were extensively drug-resistant (XDR). In the phenotypic assay, efflux pump activity was observed in 40% of isolates against multiple antibiotics mainly tigecycline, but not to imipenem. Several amino acid substitutions were detected in the regulatory genes; except in AdeN. Of note, G186V in AdeS were found to be associated with overexpression of their relative efflux pumps. No insertion sequences (ISs) were detected.Conclusions: Our findings outline the role of RND efflux pumps in resistance of A. baumannii against multiple antibiotics particularly tigecycline, and point out importance of a variety of single mutations in the corresponding regulatory systems. Even though it has been concluded that multidrug resistance occurs as a result of a complex sets of different resistant mechanisms.

scholarly journals Impact of a Cross-Kingdom Signaling Molecule of Candida albicans on Acinetobacter baumannii Physiology

2015 ◽  
Vol 60 (1) ◽  
pp. 161-167 ◽  
Author(s):  
Xenia Kostoulias ◽  
Gerald L. Murray ◽  
Gustavo M. Cerqueira ◽  
Jason B. Kong ◽  
Farkad Bantun ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cell Membrane ◽  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Defense Mechanism ◽  
Membrane Integrity ◽  
Efflux Pumps ◽  
Signaling Molecule ◽  
Content Type ◽  
Antagonistic Interactions

ABSTRACTMultidrug-resistant (MDR)Acinetobacter baumanniiis an opportunistic human pathogen that has become highly problematic in the clinical environment. Novel therapies are desperately required. To assist in identifying new therapeutic targets, the antagonistic interactions betweenA. baumanniiand the most common human fungal pathogen,Candida albicans, were studied. We have observed that theC. albicansquorum-sensing molecule, farnesol, has cross-kingdom interactions, affecting the viability ofA. baumannii. To gain an understanding of its mechanism, the transcriptional profile ofA. baumanniiexposed to farnesol was examined. Farnesol caused dysregulation of a large number of genes involved in cell membrane biogenesis, multidrug efflux pumps (AcrAB-like and AdeIJK-like), andA. baumanniivirulence traits such as biofilm formation (csuA,csuB, andompA) and motility (pilZandpilH). We also observed a strong induction in genes involved in cell division (minD,minE,ftsK,ftsB, andftsL). These transcriptional data were supported by functional assays showing that farnesol disruptsA. baumanniicell membrane integrity, alters cell morphology, and impairs virulence characteristics such as biofilm formation and twitching motility. Moreover, we showed thatA. baumanniiuses efflux pumps as a defense mechanism against this eukaryotic signaling molecule. Owing to its effects on membrane integrity, farnesol was tested to see if it potentiated the activity of the membrane-acting polymyxin antibiotic colistin. When coadministered, farnesol increased sensitivity to colistin for otherwise resistant strains. These data provide mechanistic understanding of the antagonistic interactions between diverse pathogens and may provide important insights into novel therapeutic strategies.

Biofilm Formation Restrained by Subinhibitory Concentrations of Tigecyclin in Acinetobacter baumannii Is Associated with Downregulation of Efflux Pumps

Chemotherapy ◽  
2016 ◽  
Vol 62 (2) ◽  
pp. 128-133 ◽  
Author(s):  
Huale Chen ◽  
Jianming Cao ◽  
Cui Zhou ◽  
Haiyang Liu ◽  
Xiaoxiao Zhang ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Real Time ◽  
Biofilm Formation ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Extracellular Dna ◽  
Proteinase K ◽  
Quantitative Detection ◽  
Rt Pcr ◽  
Subinhibitory Concentrations

Background: Tigecycline, one of the few therapeutic options against multidrug-resistant Acinetobacter baumannii, reaches subinhibitory serum concentrations only with cautious clinical dosing and pharmacokinetics. Subinhibitory concentrations of tigecycline might induce an A. baumannii biofilm. Methods: Biofilm formation was assessed via the crystal violet staining method. We further analyzed the main biofilm components with NaIO4, proteinase K, and DNase. Real-time RT-PCR was applied for quantitative detection of biofilm potential-associated genes. Results: In this study, A. baumannii proved to be a strong biofilm producer, and we found that proteins and extracellular DNA are crucial components of the A. baumannii biofilm. Quantitative real-time RT-PCR revealed positive correlations between biofilm formation restrained by subinhibitory concentrations of tigecycline and the expression of biofilm potential-associated genes, especially the AdeFGH efflux pump gene. Conclusion: Our results suggest that downregulation of efflux pumps, especially the AdeFGH efflux pump, is probably responsible for the decline in biofilm formation in A. baumannii treated with subinhibitory concentrations of tigecyclin.

scholarly journals Characteristics and diversity of mutations in regulatory genes of resistance-nodulation-cell division efflux pumps in association with drug-resistant clinical isolates of Acinetobacter baumannii

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Bahare Salehi ◽  
Zohreh Ghalavand ◽  
Abbas Yadegar ◽  
Gita Eslami
Keyword(s):  
Cell Division ◽  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Regulatory Genes ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Rnd Efflux Pumps ◽  
Multiple Antibiotics

Abstract Background This study was aimed to characterize the genetic diversity and expression of three putative resistance-nodulation-cell division (RND)-type efflux systems and their contribution to multidrug efflux in clinical isolates of Acinetobacter baumannii. Methods Antimicrobial susceptibility testing of 95 A. baumannii isolates was determined by Kirby-Bauer disk diffusion for 18 antibiotics and minimum inhibitory concentration (MIC) of colistin was determined by the broth microdilution method. Moreover, the MIC of five classes of antibiotics was assessed using E-test strips in the presence and absence of phenylalanine-arginine beta-naphthylamide (PAβN). Regulatory genes of the RND efflux pumps (adeRS, adeL, adeN and baeSR) were subjected to sequencing. The relative expression of adeB, adeG and adeJ genes was determined by quantitative real-time PCR (qRT-PCR). Results Overall, the majority of isolates (94%) were extensively drug-resistant (XDR). In the phenotypic assay, efflux pump activity was observed in 40% of the isolates against multiple antibiotics mainly tigecycline. However, we found no efflux activity against imipenem. Several amino acid substitutions were detected in the products of regulatory genes; except in AdeN. Of note, G186V mutation in AdeS was found to be associated with overexpression of its efflux pump. No insertion sequences were detected. Conclusions Our findings outlined the role of RND efflux pumps in resistance of A. baumannii to multiple antibiotics particularly tigecycline, and pointed out the importance of a variety of single mutations in the corresponding regulatory systems. Further studies are required to decipher the precise role of RND efflux pumps in multidrug-resistant clinical isolates of A. baumannii.

scholarly journals Biofilm Formation and blaOXA Genes Detection Among Acinetobacter baumannii from Clinical Isolates in a Tertiary Care Kirtipur Hospital, Nepal

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Upasana Ghimire ◽  
Rupesh Kandel ◽  
Mary Neupane ◽  
Sanjit Shrestha ◽  
Sudeep K C ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Tertiary Care ◽  
Carbapenem Resistance ◽  
Diffusion Method ◽  
Clinical Samples ◽  
Resistance Pattern ◽  
Clinical Settings ◽  
Drug Resistance Pattern ◽  
Acinetobacter Spp

(1) Background: Acinetobacter baumannii has emerged as a leading cause of nosocomial infections as they are capable of evolving resistance to various classes of antibiotics. The ability of A. baumannii to form biofilm might also be associated with increased antibiotic resistance and hence treatment failure. This study was carried to associate the biofilm formation with the drug resistance pattern of A. baumannii and to detect blaOXA-23, blaOXA-24, and blaOXA-51 from carbapenem resistance isolates. (2) Methods: Among different clinical samples, a total of 19 Acinetobacter spp. were identified with conventional microbiological procedures. The biofilm production was determined by a quantitative adherence assay. The antimicrobial susceptibility test was carried out by the Kirby-Bauer disc diffusion method, carbapenemase production detection was confirmed by Modified Hodge Test. And target resistant genes were detected by polymerase chain reaction. (3) Results: Out of 90 clinical specimens, 64.44% (58/90) showed bacterial growth. Whereas, 32.75% (19/58) isolates were identified as A. baumannii. Among all A. baumannii isolates, 84.21% (16/19) were multidrug-resistance and 63.16% (12/19) carbapenem resistance phenotypically. blaOXA-51 was detected in all the isolates and blaOXA-23 was detected only in 63.16% (12/19) isolates. However, blaOXA-24 was not detected in any of the isolates. Among A. baumannii, 89.47% (17/19) isolates produced biofilm with 47.37% (9/19) strong biofilm producers. (4) Conclusions: In the majority of MDR A. baumannii, blaOXA-51 and blaOXA-23 were detected as the determinant factor for carbapenem resistance having a direct relation with biofilm formation. This study provided a valuable clue for the management of A. baumannii infections in clinical settings.  

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