scholarly journals Histone-like nucleoid-structuring protein (H-NS) regulatory role in antibiotic resistance in Acinetobacter baumannii

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Deja Rodgers ◽  
Casin Le ◽  
Camila Pimentel ◽  
Marisel R. Tuttobene ◽  
Tomás Subils ◽  
...  

AbstractIn the multidrug resistant (MDR) pathogen Acinetobacter baumannii the global repressor H-NS was shown to modulate the expression of genes involved in pathogenesis and stress response. In addition, H-NS inactivation results in an increased resistance to colistin, and in a hypermotile phenotype an altered stress response. To further contribute to the knowledge of this key transcriptional regulator in A. baumannii behavior, we studied the role of H-NS in antimicrobial resistance. Using two well characterized A. baumannii model strains with distinctive resistance profile and pathogenicity traits (AB5075 and A118), complementary transcriptomic and phenotypic approaches were used to study the role of H-NS in antimicrobial resistance, biofilm and quorum sensing gene expression. An increased expression of genes associated with β-lactam resistance, aminoglycosides, quinolones, chloramphenicol, trimethoprim and sulfonamides resistance in the Δhns mutant background was observed. Genes codifying for efflux pumps were also up-regulated, with the exception of adeFGH. The wild-type transcriptional level was restored in the complemented strain. In addition, the expression of biofilm related genes and biofilm production was lowered when the transcriptional repressor was absent. The quorum network genes aidA, abaI, kar and fadD were up-regulated in Δhns mutant strains. Overall, our results showed the complexity and scope of the regulatory network control by H-NS (genes involved in antibiotic resistance and persistence). These observations brings us one step closer to understanding the regulatory role of hns to combat A. baumannii infections.

2021 ◽  
Author(s):  
Deja Rodgers ◽  
Casin Le ◽  
Camila Pimentel ◽  
Marisel Romina Tuttobene ◽  
Tomás Subils ◽  
...  

Abstract In the multidrug resistant (MDR) pathogen Acinetobacter baumannii the global repressor H-NS was shown to modulate the expression of genes related to quorum sensing, biosynthetic pathways, cell adhesion, virulence, and autotransporters. In addition, H-NS is involved in stress response and its inactivation results in an increased resistance to colistin, and in a hypermotile phenotype an altered stress response. To further contribute to the knowledge of this key transcriptional regulator in A. baumannii behavior, we studied the role of H-NS in antimicrobial resistance. Using two well characterized A. baumannii model strains with distinctive resistance profile and pathogenicity traits (AB5075 and A118), complementary transcriptomic and phenotypic approaches were used to study the role of H-NS in antimicrobial resistance, biofilm and quorum sensing gene expression. An increased expression of genes associated with β-lactam resistance, aminoglycosides, quinolones, chloramphenicol, trimethoprim and sulfonamides resistance in the Δhns mutant background was observed. Genes codifying for efflux pumps were also up-regulated, with the exception of adeFGH. The wild-type transcriptional level was restored in the complemented strain. In addition, the expression of biofilm related genes and biofilm production was lowered when the transcriptional repressor was absent. The quorum network genes aidA, abaI, kar and fadD were up-regulated in Δhns mutant strains. Overall, our results showed the complexity and scope of the regulatory network control by H-NS (genes involved in antibiotic resistance and persistence). These observations brings us one step closer to understanding the regulatory role of hns to combat A. baumannii infections.


2011 ◽  
Vol 60 (2) ◽  
pp. 211-215 ◽  
Author(s):  
B. S. Lopes ◽  
A. Hamouda ◽  
J. Findlay ◽  
S. G. B. Amyes

Acinetobacter baumannii is a Gram-negative pathogenic bacterium that often exhibits a multidrug-resistant phenotype causing infections at various sites of the body and increasingly leading to septicaemic shock. This study evaluated the role of acriflavine, a frameshift mutagen, on the movement of insertion sequence ISAba1 in clinical isolates of A. baumannii, with the focus on changes in expression levels of the bla ADC and bla OXA-51-like genes. Resistance profiles were assessed with consideration of ISAba1 acting as a promoter upstream of the bla ADC or bla OXA-51-like gene. ISAba1 movement was observed in the acriflavine mutants Ab153M and Ab1225M. Ab153M exhibited an increase in the MIC values of carbapenems and ceftazidime, with ISAba1 gained upstream of the bla ADC and bla OXA-51-like genes, correlating with an increase in gene expression. Reduced expression of the 17, 23 and 25 kDa outer-membrane proteins (OMPs) was also observed in Ab153M. There was a significant decrease in MIC values of carbapenems with the loss of ISAba1 upstream of the bla ADC and bla OXA-51-like genes in strain Ab1225M, and a significant decrease in bla OXA-51-like gene expression and, to a lesser extent, in bla ADC expression. Ab1225M and a serially subcultured Ab1225 strain (Ab1225s) exhibited overexpression of the 17, 23, 25 and 27 kDa OMPs. There was a decrease in MIC values of the carbapenems and piperacillin/tazobactam but not of ceftazidime in Ab1225s, which had ISAba1 upstream of the bla ADC and bla OXA-51-like genes. A significant decrease in bla OXA-51-like expression was observed in Ab1225s, whereas the expression of bla ADC was similar to that in the Ab1225 parental strain. The attenuation in this strain may be due to overexpression of OMPs and it is clear that, even if ISAba1 is present upstream of an antibiotic resistance gene, it may not necessarily contribute towards the overexpression of antibiotic resistance genes (bla OXA-51-like in Ab1225s). Movement of the IS element within the A. baumannii chromosome may be an important regulatory mechanism employed by the bacterium under particular stress conditions, and the ability to upregulate the expression of antibiotic resistance genes is likely to be an important factor in the pathogenicity of this bacterium.


Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 817
Author(s):  
Abebe Mekuria Shenkutie ◽  
Mian Zhi Yao ◽  
Gilman Kit-hang Siu ◽  
Barry Kin Chung Wong ◽  
Polly Hang-mei Leung

In order to understand the role of biofilm in the emergence of antibiotic resistance, a total of 104 clinical Acinetobacter baumannii strains were investigated for their biofilm-forming capacities and genes associated with biofilm formation. Selected biofilm-formers were tested for antibiotic susceptibilities when grown in biofilm phase. Reversibility of antibiotic susceptibility in planktonic cells regrown from biofilm were investigated. We found 59.6% of the strains were biofilm-formers, among which, 66.1% were non-multidrug resistant (MDR) strains. Presence of virulence genes bap, csuE, and abaI was significantly associated with biofilm-forming capacities. When strains were grown in biofilm state, the minimum biofilm eradication concentrations were 44, 407, and 364 times higher than the minimum bactericidal concentrations (MBC) for colistin, ciprofloxacin, and imipenem, respectively. Persisters were detected after treating the biofilm at 32–256 times the MBC of planktonic cells. Reversibility test for antibiotic susceptibility showed that biofilm formation induced reversible antibiotic tolerance in the non-MDR strains but a higher level of irreversible resistance in the extensively drug-resistant (XDR) strain. In summary, we showed that the non-MDR strains were strong biofilm-formers. Presence of persisters in biofilm contributed to the reduced antibiotic susceptibilities. Biofilm-grown Acinetobacter baumannii has induced antibiotic tolerance in non-MDR strains and increased resistance levels in XDR strains. To address the regulatory mechanisms of biofilm-specific resistance, thorough investigations at genome and transcription levels are warranted.


2020 ◽  
Author(s):  
Fanny Huang ◽  
Noelle Fitchett ◽  
Chelsea Razo-Gutierrez ◽  
Casin Le ◽  
Grace Ra ◽  
...  

AbstractDisruption of the histone-like nucleoid structuring protein (H-NS) was shown to affect the ability for Gram-negative bacteria to regulate genes associated with virulence, persistence, stress response, quorum sensing, biosynthesis pathways and cell adhesion. Here, we used the expression of metallo-β-lactamases (MBLs) known to elicit envelope stress by the accumulation of toxic species in the periplasm to interrogate the role of H-NS in Acinetobacter baumannii, together with other stressors. Using a multidrug-resistant A. baumannii, we observed that H-NS plays a role in alleviating the stress triggered by MBL toxic precursors and counteract the effect of DNA-damaging agents, supporting its role in stress response.ImportanceCarbapenem-resistant A. baumannii (CRAB) is recognized as one of the most threatening gram-negative bacilli. H-NS is known to play a role in controlling the transcription of a variety of different genes, including those associated with stress response, persistence and virulence. In the present work, we uncovered a link between the role of H-NS in the A. baumannii stress response and its relationship with the envelope stress response and resistance to DNA-damaging agents. Overall, we posit a new role of H-NS, showing that H-NS serves to endure envelope stress that could also be a mechanism that alleviates the stress induced by MBL expression in A. baumannii. This could be an evolutionary advantage to further resist the action of carbapenems.


2013 ◽  
Vol 58 (3) ◽  
pp. 1806-1808 ◽  
Author(s):  
Younes Smani ◽  
Anna Fàbrega ◽  
Ignasi Roca ◽  
Viviana Sánchez-Encinales ◽  
Jordi Vila ◽  
...  

ABSTRACTAcinetobacter baumanniihas emerged as a nosocomial pathogen with an increased prevalence of multidrug-resistant strains. The role of the outer membrane protein A (OmpA) in antimicrobial resistance remains poorly understood. In this report, disruption of theompAgene led to decreased MICs of chloramphenicol, aztreonam, and nalidixic acid. We have characterized, for the first time, the contribution of OmpA in the antimicrobial resistance phenotype ofA. baumannii.


mSphere ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Fanny Huang ◽  
Noelle Fitchett ◽  
Chelsea Razo-Gutierrez ◽  
Casin Le ◽  
Jasmine Martinez ◽  
...  

ABSTRACT Disruption of the histone-like nucleoid structuring protein (H-NS) was shown to affect the ability of Gram-negative bacteria to regulate genes associated with virulence, persistence, stress response, quorum sensing, biosynthesis pathways, and cell adhesion. Here, we used the expression of metallo-β-lactamases (MBLs), known to elicit envelope stress by the accumulation of toxic precursors in the periplasm, to interrogate the role of H-NS in Acinetobacter baumannii, together with other stressors. Using a multidrug-resistant A. baumannii strain, we observed that H-NS plays a role in alleviating the stress triggered by MBL toxic precursors and counteracts the effect of DNA-damaging agents, supporting its role in stress response. IMPORTANCE Carbapenem-resistant A. baumannii (CRAB) is recognized as one of the most threatening Gram-negative bacilli. H-NS is known to play a role in controlling the transcription of a variety of different genes, including those associated with the stress response, persistence, and virulence. In the present work, we uncovered a link between the role of H-NS in the A. baumannii stress response and its relationship with the envelope stress response and resistance to DNA-damaging agents. Overall, we posit a new role of H-NS, showing that H-NS serves to endure envelope stress and could also be a mechanism that alleviates the stress induced by MBL expression in A. baumannii. This could be an evolutionary advantage to further resist the action of carbapenems.


2020 ◽  
Vol 20 (2) ◽  
pp. 160-166
Author(s):  
Seyedeh Hanieh Eshaghi Zadeh ◽  
Hossein Fahimi ◽  
Fatemeh Fardsanei ◽  
Mohammad Mehdi Soltan Dallal

Background: Salmonellosis is a major food-borne disease worldwide. The increasing prevalence of antimicrobial resistance among food-borne pathogens such as Salmonella spp. is concerning. Objective: The main objective of this study is to identify class 1 integron genes and to determine antibiotic resistance patterns among Salmonella isolates from children with diarrhea. Methods: A total of 30 Salmonella isolates were recovered from children with diarrhea. The isolates were characterized for antimicrobial susceptibility and screened for the presence of class 1 integron genes (i.e. intI1, sulI1, and qacEΔ1). Results: The most prevalent serotype was Enteritidis 36.7%, followed by Paratyphi C (30%), and Typhimurium (16.7%). The highest rates of antibiotic resistance were obtained for nalidixic acid (53.3%), followed by streptomycin (40%), and tetracycline (36.7%). Regarding class 1 integrons, 36.7%, 26.7%, and 33.3% of the isolates carried intI1, SulI, and qacEΔ1, respectively, most of which (81.8%) were multidrug-resistant (MDR). Statistical analysis revealed that the presence of class 1 integron was significantly associated with resistance to streptomycin and tetracycline (p = 0.042). However, there was no association between class 1 integron and other antibiotics used in this study (p > 0.05). Conclusion: The high frequency of integron class 1 gene in MDR Salmonella strains indicates that these mobile genetic elements are versatile among different Salmonella serotypes, and associated with reduced susceptibility to many antimicrobials.


Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 671
Author(s):  
Federica Giacometti ◽  
Hesamaddin Shirzad-Aski ◽  
Susana Ferreira

Antimicrobial resistance (AMR) is a global problem and there has been growing concern associated with its widespread along the animal–human–environment interface. The farm-to-fork continuum was highlighted as a possible reservoir of AMR, and a hotspot for the emergence and spread of AMR. However, the extent of the role of non-antibiotic antimicrobials and other food-related stresses as selective factors is still in need of clarification. This review addresses the use of non-antibiotic stressors, such as antimicrobials, food-processing treatments, or even novel approaches to ensure food safety, as potential drivers for resistance to clinically relevant antibiotics. The co-selection and cross-adaptation events are covered, which may induce a decreased susceptibility of foodborne bacteria to antibiotics. Although the available studies address the complexity involved in these phenomena, further studies are needed to help better understand the real risk of using food-chain-related stressors, and possibly to allow the establishment of early warnings of potential resistance mechanisms.


Author(s):  
M.A.A. Machado ◽  
W.A. Ribeiro ◽  
V.S. Toledo ◽  
G.L.P.A. Ramos ◽  
H.C. Vigoder ◽  
...  

Background: Milk is a reservoir for several groups of microorganisms, which may pose health risks. The aim of this work was to assess the antibiotic resistance and biofilm production in catalase-positive Gram-positive cocci isolated from Brazilian pasteurized milk. Methods: The bacteria were isolated using Baird-Parker agar and identified by MatrixAssisted Laser Desorption/Ionization-Time-Of-Flight (MALDI-TOF) mass spectrometer. Disk diffusion technique was used to evaluate antimicrobial susceptibility. For qualitative evaluation of biofilm production, the growth technique was used on Congo Red Agar. Results: Totally, 33 out of 64 isolates were identified, including Staphylococcus epidermidis (n=3; 4.7%), Macrococcus caseolyticus (n=14; 21.9%), and Kocuria varians (n=16; 25%). Twenty-two isolates were resistant to at least one antibiotic. Biofilm production was detected in only 5 isolates of K. varians and 1 isolate of S. epidermidis. All 14 M. caseolyticus isolates were resistant to at least one antibiotic; but, multidrug resistant (MDR) isolates were not detected. Among all K. varians isolates, 4 were resistant to at least one antibiotic from three different classes and were considered to be MDR. Conclusion: The presence of antibiotic-resistant M. caseolyticus, S. epidermidis, and K. varians isolates, especially MDRs, in milk samples highlights the possible role of milk as a reservoir of resistance genes


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