scholarly journals Biofilm-Induced Antibiotic Resistance in Clinical Acinetobacter baumannii Isolates

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 ◽  
Vol 10 (1) ◽  
Author(s):  
Udomluk Leungtongkam ◽  
Rapee Thummeepak ◽  
Thawatchai Kitti ◽  
Kannipa Tasanapak ◽  
Jintana Wongwigkarn ◽  
...  

Abstract In this study, we examined the association between antimicrobial resistance, CRISPR/Cas systems and virulence with phage susceptibility in Acinetobacter baumannii and investigated draft genomes of phage susceptible multidrug resistant A. baumannii strains from Thailand. We investigated 230 A. baumannii strains using 17 lytic A. baumannii phages and the phage susceptibility was 46.5% (107/230). Phage susceptibility was also associated with resistance to numerous antibiotics (p-value < 0.05). We also found association between biofilm formation and the presence of ompA gene among phage susceptible A. baumannii strains (p-value < 0.05). A. baumannii isolates carrying cas5 or combinations of two or three other cas genes, showed a significant increase in phage resistance. Whole-genome sequences of seven phage susceptible A. baumannii isolates revealed that six groups of antibiotic resistance genes were carried by all seven phage susceptible A. baumannii. All strains carried biofilm associated genes and two strains harbored complete prophages, acquired copper tolerance genes, and CRISPR-associated (cas) genes. In conclusion, our data exhibits an association between virulence determinants and biofilm formation among phage susceptible A. baumannii strains. These data help to understand the bacterial co-evolution with phages.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Umarani Brahma ◽  
Paresh Sharma ◽  
Shweta Murthy ◽  
Savitri Sharma ◽  
Shalini Chakraborty ◽  
...  

Abstract Methicillin-Resistant Staphylococcus aureus (MRSA) is a significant threat to human health. Additionally, biofilm forming bacteria becomes more tolerant to antibiotics and act as bacterial reservoir leading to chronic infection. In this study, we characterised the antibiotic susceptibility, biofilm production and sequence types (ST) of 74 randomly selected clinical isolates of S. aureus causing ocular infections. Antibiotic susceptibility revealed 74% of the isolates as resistant against one or two antibiotics, followed by 16% multidrug-resistant isolates (MDR), and 10% sensitive. The isolates were characterized as MRSA (n = 15), Methicillin-sensitive S. aureus (MSSA, n = 48) and oxacillin susceptible mecA positive S. aureus (OS-MRSA, n = 11) based on oxacillin susceptibility, mecA gene PCR and PBP2a agglutination test. All OS-MRSA would have been misclassified as MSSA on the basis of susceptibility test. Therefore, both phenotypic and genotypic tests should be included to prevent strain misrepresentation. In addition, in-depth studies for understanding the emerging OS-MRSA phenotype is required. The role of fem XAB gene family has been earlier reported in OS-MRSA phenotype. Sequence analysis of the fem XAB genes revealed mutations in fem × (K3R, H11N, N18H and I51V) and fem B (L410F) genes. The fem XAB genes were also found down-regulated in OS-MRSA isolates in comparison to MRSA. In OS-MRSA isolates, biofilm formation is regulated by fibronectin binding proteins A & B. Molecular typing of the isolates revealed genetic diversity. All the isolates produced biofilm, however, MRSA isolates with strong biofilm phenotype represent a worrisome situation and may even result in treatment failure.


Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1115
Author(s):  
Hui-Ling Lin ◽  
Chen-En Chiang ◽  
Mei-Chun Lin ◽  
Mei-Lan Kau ◽  
Yun-Tzu Lin ◽  
...  

Limited therapeutic options are available for multidrug-resistant Acinetobacter baumannii (MDR-AB), and the development of effective treatments is urgently needed. The efficacy of four aerosolized antibiotics (gentamicin, amikacin, imipenem, and meropenem) on three different MDR-AB strains was evaluated using hypertonic saline (HS, 7 g/100 mL) as the aerosol carrier. HS aerosol effectively hindered biofilm formation by specific MDR-AB strains. It could also interrupt the swarming dynamics of MDR-AB and the production of extracellular polymeric substances, which are essential for biofilm progression. Biofilms protect the microorganisms from antibiotics. The use of HS aerosol as a carrier resulted in a decreased tolerance to gentamicin and amikacin in the biofilm-rich MDR-AB. Moreover, we tested the aerosol characteristics of antibiotics mixed with HS and saline, and results showed that HS enhanced the inhaled delivery dose with a smaller particle size distribution of the four antibiotics. Our findings demonstrate the potential of using “old” antibiotics with our “new” aerosol carrier, and potentiate an alternative therapeutic strategy to eliminate MDR-AB infections from a biofilm-disruption perspective.


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.


Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 630 ◽  
Author(s):  
Aisha M. Alamri ◽  
Afnan A. Alsultan ◽  
Mohammad A. Ansari ◽  
Amani M. Alnimr

This study analyzed the genotype, antibiotic resistance, and biofilm formation of Acinetobacter baumannii strains and assessed the correlation between biofilm formation, antibiotic resistance, and biofilm-related risk factors. A total of 207 non-replicate multi-drug-resistant A. baumannii strains were prospectively isolated. Phenotypic identification and antimicrobial susceptibility testing were carried out. Isolate biofilm formation ability was evaluated using the tissue culture plate (TCP), Congo red agar, and tube methods. Clonal relatedness between the strains was assessed by enterobacterial repetitive intergenic consensus-PCR genotyping. Of the 207 isolates, 52.5% originated from an intensive care unit setting, and pan resistance was observed against ceftazidime and cefepime, with elevated resistance (99–94%) to piperacillin/tazobactam, imipenem, levofloxacin, and ciprofloxacin. alongside high susceptibility to tigecycline (97.8%). The Tissue culture plate, Tube method, and Congo red agar methods revealed that 53.6%, 20.8%, and 2.7% of the strains were strong biofilm producers, respectively, while a significant correlation was observed between biofilm formation and device-originating respiratory isolates (p = 0.0009) and between biofilm formation in colonized vs. true infection isolates (p = 0.0001). No correlation was detected between antibiotic resistance and biofilm formation capacity, and the majority of isolates were clonally unrelated. These findings highlight the urgent need for implementing strict infection control measures in clinical settings.


Author(s):  
Eugene A. Sheck ◽  
Mikhail V. Edelstein ◽  
Marina V. Sukhorukova ◽  
Natali V. Ivanchik ◽  
Elena Yu. Skleenova ◽  
...  

A high level of resistance to carbapenems in Acinetobacter baumannii strains severely limits therapeutic possibilities. Colistin is the last resort drug against such strains, although the cases of resistance to this drug have become more frequent. This article presents the epidemiological features and genetic diversity of colistin nonsusceptible A. baumannii strains collected as part of a national multicenter epidemiological study of the antibiotic resistance of pathogens of nosocomial infections (MARATHON), which was conducted in 2013-2014 in Russia. A total of 527 A. baumannii isolates were collected, 10 (1.9%) of which were nonsusceptible to colistin. The majority of nonsusceptible A. baumannii isolates to colistin showed resistance to carbapenems and had the genes of the acquired OXA-40-like carbapenemases (n=6). In one case, a combination of OXA-23-like + OXA-40-like (n=1) genes was identified. One strain had the multidrug-resistant (MDR) phenotype, 6 isolates had extensively drug-resistant (XDR) phenotype, and 3 isolates had pandrug-resistant (PDR) phenotype. Among the colistin nonsusceptible A. baumannii isolates, 6 individual genotypes were identified, most of which belonged to successful international clones (CC92OXF/CC2PAS, n=4; CC944OXF/ST78PAS, n=4; CC109OXF/CC1PAS, n=1).


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.


Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 833
Author(s):  
Camila Pimentel ◽  
Casin Le ◽  
Marisel R. Tuttobene ◽  
Tomas Subils ◽  
Krisztina M. Papp-Wallace ◽  
...  

Acinetobacter baumannii has become a serious threat to human health due to its extreme antibiotic resistance, environmental persistence, and capacity to survive within the host. Two A. baumannii strains, A118 and AB5075, commonly used as model systems, and three carbapenem-resistant strains, which are becoming ever more dangerous due to the multiple drugs they can resist, were exposed to 3.5% human serum albumin (HSA) and human serum (HS) to evaluate their response with respect to antimicrobial resistance, biofilm formation, and quorum sensing, all features responsible for increasing survival and persistence in the environment and human body. Expression levels of antibiotic resistance genes were modified differently when examined in different strains. The cmlA gene was upregulated or downregulated in conditions of exposure to 3.5% HSA or HS depending on the strain. Expression levels of pbp1 and pbp3 tended to be increased by the presence of HSA and HS, but the effect was not seen in all strains. A. baumannii A118 growing in the presence of HS did not experience increased expression of these genes. Aminoglycoside-modifying enzymes were also expressed at higher or lower levels in the presence of HSA or HS. Still, the response was not uniform; in some cases, expression was enhanced, and in other cases, it was tapered. While A. baumannii AB5075 became more susceptible to rifampicin in the presence of 3.5% HSA or HS, strain A118 did not show any changes. Expression of arr2, a gene involved in resistance to rifampicin present in A. baumannii AMA16, was expressed at higher levels when HS was present in the culture medium. HSA and HS reduced biofilm formation and production of N-Acyl Homoserine Lactone, a compound intimately associated with quorum sensing. In conclusion, HSA, the main component of HS, stimulates a variety of adaptative responses in infecting A. baumannii strains.


2016 ◽  
Vol 4 (2) ◽  
Author(s):  
Bhavani Manivannan ◽  
Niranjana Mahalingam ◽  
Sudhir Jadhao ◽  
Amrita Mishra ◽  
Pravin Nilawe ◽  
...  

We present the draft genome assembly of an extensively drug-resistant (XDR) Pseudomonas aeruginosa strain isolated from a patient with a history of genito urinary tuberculosis. The draft genome is 7,022,546 bp with a G+C content of 65.48%. It carries 7 phage genomes, genes for quorum sensing, biofilm formation, virulence, and antibiotic resistance.


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