Antimicrobial Resistance In Acinetobacter Baumannii Research Articles

Exploring the resistome and virulome in major sequence types of Acinetobacter baumannii genomes: Correlations with genome divergence and sequence types

The increasing global prevalence of antimicrobial resistance in Acinetobacter baumannii has led to concerns regarding the effectiveness of infection treatment. Moreover, the critical role of virulence factor genes in A. baumannii's pathogenesis and its propensity to cause severe disease is of particular importance. Comparative genomics, including multi-locus sequence typing (MLST), enhances our understanding of A. baumannii epidemiology. While there is substantial documentation on A. baumannii, a comprehensive study of the antibiotic-resistant mechanisms and the virulence factors contributing to pathogenesis, and their correlation with Sequence Types (STs) remains incompletely elucidated. In this study, we aim to explore the relationship between antimicrobial resistance genes, virulence factor genes, and STs using genomic data from 223 publicly available A. baumannii strains. The core phylogeny analysis revealed five predominant STs in A. baumannii genomes, linked to their geographical sources of isolation. Furthermore, the resistome and virulome of A. baumannii followed an evolutionary pattern consistent with their pan-genome evolution. Among the major STs, we observed significant variations in resistant genes against “aminoglycoside” and “sulphonamide” antibiotics, highlighting the role of genotypic variations in determining resistance profiles. Furthermore, the presence of virulence factor genes, particularly exotoxin and nutritional / metabolic factor genes, played a crucial role in distinguishing the major STs, suggesting a potential link between genetic makeup and pathogenicity. Understanding these associations can provide valuable insights into A. baumannii's virulence potential and clinical outcomes, enabling the development of effective strategies to combat infections caused by this opportunistic pathogen.

Naturally derived efflux pump inhibitor among tetracycline-resistant Acinetobacter baumannii isolates

Abstract Background: The antimicrobial resistance of Acinetobacter baumannii is of major concern. It is one of the commonly distributed nosocomial pathogens, and its strains are frequently reported to demonstrate resistance to the most routinely prescribed antibiotics in varying degrees. Objective: This study aimed to detect the inhibitory effect of chamomile extract against the efflux pump of A. baumannii. Materials and Methods: Clinical samples (125) were collected from different sites (urine, sputum, wound, and burn swabs), followed by A. baumannii isolation and identification, and detection of tetracycline susceptibility test by disk-diffusion. Later on bacterial efflux pump activity was detected by ethidium bromide cartwheel assay and water extract of chamomile was used as an inhibitor of efflux pump A. baumannii. Results: The percentage of A. baumannii isolation 23/125 (18.4%) that distributed as 25% isolates were obtained from sputum, 17.9% isolates from burns, whereas 16% and 12.5% isolates from urine and wounds respectively. It showed various resistances against different members of the three generations of tetracyclines, with the highest resistance against minocycline 47.8% followed by resistance to tetracycline and doxycycline as 43.5% and 39%, respectively. Efflux pump was detected in all cases, water extract of chamomile showed a significant inhibitory effect especially at 80 mg/mL concentration. Conclusion: Efflux pump is an important mechanism for tetracycline resistance among A. baumannii isolates, and the watery extract of chamomile can be considered a prompt inhibitor for this pump.

Restriction-methylation systems regulate transformation in Acinetobacter baumannii.

Antimicrobial resistance in Acinetobacter baumannii is a major concern. Natural transformation remains understudied as a horizontal gene transfer (HGT) mechanism for the spread of resistance genes. Recent work (Vesel et al.) reveals a profound impact of the state of donor DNA methylation with strong implications for HGT of resistance determinants in this worrisome pathogen.

Effect of traditional Chinese medicine monomers interfering with quorum-sensing on virulence factors of extensively drug-resistant Acinetobacter baumannii.

The antimicrobial resistance of Acinetobacter baumannii (A. baumannii) clinical isolates has emerged as a great threat to public health. Quorum sensing (QS) is one of the resistance mechanisms for drug-resistant A. baumannii. Interfering with QS is a promising strategy to combat infections caused by drug-resistant bacteria. This study explored the QS inhibition ability of thirty-four traditional Chinese medicine monomers (TCMMs) and assessed the effect of QS inhibitors (QSIs) on the virulence factors of twelve extensively drug-resistant A. baumannii (XDRAB) strains. Nine traditional Chinese medicine monomers, such as caffeic acid, cinnamic acid, and myricetin, were found to be able to inhibit the bacterial QS. Then, at 1/8 of the minimal inhibitory concentration, we found that these QSIs inhibited extensively drug-resistant A. baumannii adhesion and biofilm formation and downregulated the expression levels of virulence-associated genes (abaI, abaR, csuE, pgaA, and bap). In conclusion, nine traditional Chinese medicine monomers have QS inhibitory activity and may downregulate QS genes to interfere with the QS system, which could inhibit the expression of extensively drug-resistant A. baumannii virulence factors. These results suggest that traditional Chinese medicine monomers could develop as novel anti-virulence compounds to control extensively drug-resistant A. baumannii infections.

A Six-Year Retrospective Study of Microbiological Characteristics and Antimicrobial Resistance in Specimens from a Tertiary Hospital's Surgical Ward.

Surgery has revolutionized the practice of medicine by allowing the treatment of conditions amenable to conservative medical management with some of them pathophysiologically involving the prevalence of pathogenic microorganisms. On the other hand, infections such as surgical site infections or urinary tract infections may complicate patients hospitalized in surgical wards leading to considerable morbidity, mortality, and increased healthcare-associated costs. The aim of this study was to present the microbiological characteristics and antimicrobial resistance of all isolates identified in microbiological specimens from a surgical ward of a tertiary hospital in Greece during a six-year period. Only specimens that yielded at least one microorganism were included in the analysis. In total, 1459 strains in 789 positive cultures were isolated. The most common sample sent to the microbiology department was pus from surgical wounds. The most common pathogens among all 1459 strains isolated were Enterobacterales at 33% (n = 482), however, the most common genus was Enterococcus at 22.3% (n = 326). Antimicrobial resistance against third-generation cephalosporins was 23% (n = 111/482) among Enterobacterales, while, the rate of vancomycin-resistant enterococci (VRE) was 18.5% (n = 60/324) among Enterococcus species and was increasing in the last years of the study. Antimicrobial resistance of Acinetobacter baumannii to carbapenems was 68.8% (n = 11/16), which was lower than the corresponding rate in other wards in Greece. The antimicrobial resistance rates noted herein raise questions regarding the appropriateness of currently suggested antimicrobials in guidelines and imply that a revision could be required. Practicing clinicians should always be aware of local microbiological data that allow the selection of appropriate antimicrobials for the management of infections. Finally, the increasing rates of VRE noted herein mandate further actions from the point of infection control and antimicrobial stewardship.

Prevalence and Resistance Profile of Acinetobacter baumannii Isolated from Clinical Specimens at a Tertiary Care Hospital in Bangladesh

Background: Acinetobacter baumannii is one of the significant pathogens to cause healthcare-associated infections worldwide. It is difficult to control and the infections caused by it are difficult to treat, because it is multidrug resistant.
 Objective: This study was conducted to determine the prevalence and antimicrobial resistance pattern of Acinetobacter baumannii at Dhaka Medical College Hospital, Dhaka, Bangladesh over a 12 months period.
 Methodology: This retrospective study was carried out over a period of one year from July 2014 to June 2015 in the department of Microbiology at Dhaka Medical College Hospital, Dhaka, Bangladesh. Antimicrobial susceptibility testing of the isolates was performed by the disk diffusion method as recommended by Clinical Laboratory and Standards Institute CLSI.
 Results: Non duplicate 28 A. baumannii were isolated out of a total 191 pathogenic Gram negative isolates (14.66% prevalence). The most frequently isolated A. baumannii was from ICU patients (75%) followed by inpatients (18%) and outpatients (7%). Most of the isolates were recovered from tracheal aspirates (75%). The resistance rates were higher than most of the internationally reported levels. Cephalosporins, aminoglycosides, fluoroquinolones and even carbapenems are becoming practically ineffective, where the colistin elicited the highest susceptibility levels.
 Conclusion: This study has guided the empirical therapy and suggest that surveillance of antimicrobial resistance of Acinetobacter baumannii is necessary.
 Journal of National Institute of Neurosciences Bangladesh, July 2021, Vol. 7, No. 2, pp. 177-180

The Involvement of the csy1 Gene in the Antimicrobial Resistance of Acinetobacter baumannii.

Acinetobacter baumannii is an important, opportunistic nosocomial pathogen that causes a variety of nosocomial infections, and whose drug resistance rate has increased in recent years. The CRISPR-Cas system exists in several bacteria, providing adaptive immunity to foreign nucleic acid invasion. This study explores whether CRISPR-Cas is related to drug resistance. Antibiotics were used to treat strains ATCC19606 and AB43, and the expression of CRISPR-related genes was found to be changed. The Csy proteins (Csy1–4) were previously detected to promote target recognition; however, the potential function of csy1 gene is still unknown. Thus, the RecAb homologous recombination system was utilized to knock out the csy1 gene from A. baumannii AB43, which carries the Type I-Fb CRISPR-Cas system, and to observe the drug resistance changes in wild-type and csy1-deleted strains. The AB43Δcsy1 mutant strain was found to become resistant to antibiotics, while the wild-type strain was sensitive to antibiotics. Moreover, transcriptome analysis revealed that the csy1 gene regulates genes encoding CRISPR-Cas-related proteins, drug-resistant efflux pumps, membrane proteins, and oxidative phosphorylation-related proteins, inhibiting antimicrobial resistance in A. baumannii. The in vitro resistance development assay revealed that the complete CRISPR-Cas system could inhibit the development of bacterial resistance. Our findings expand our understanding of the role of CRISPR-Cas csy1 gene in A. baumannii and link the CRISPR-Cas system to the biogenesis of bacterial drug-resistant structures.

Screening of small molecules attenuating biofilm formation of Acinetobacter baumannii by inhibition of ompA promoter activity.

Anti-virulence therapeutic strategies are promising alternatives against drug-resistant pathogens. Outer membrane protein A (OmpA) plays a versatile role in the pathogenesis and antimicrobial resistance of Acinetobacter baumannii. Therefore, OmpA is an innovative target for anti-virulence therapy against A. baumannii. This study aimed to develop a high-throughput screening (HTS) system to discover small molecules inhibiting the ompA promoter activity of A. baumannii and screen chemical compounds using the bacterial growth-based HTS system. The ompA promoter and open reading frame of nptI fusion plasmids that controlled the expression of nptI encoding resistance to kanamycin by the ompA promoter were constructed and then transformed into A. baumannii ATCC 17978. This reporter strain was applied to screen small molecules inhibiting the ompA promoter activity in a chemical library. Of the 7,520 chemical compounds, 15 exhibited ≥ 70% growth inhibition of the report strain cultured in media containing kanamycin. Three compounds inhibited the expression of ompA and OmpA in the outer membrane of A. baumannii ATCC 17978, which subsequently reduced biofilm formation. In conclusion, our reporter strain is useful for large-scale screening of small molecules inhibiting the ompA expression in A. baumannii. Hit compounds identified by the HTS system are promising scaffolds to develop novel therapeutics against A. baumannii.

The First Report of the Antimicrobial Resistance of Acinetobacter baumannii Isolates from Seafood Samples

Acinetobacterbaumannii is a newly-launched bacterium responsible for rare cases of diarrhea and foodborne diseases. This survey was performed to study the prevalence and antimicrobial resistance of A. baumannii isolates recovered from fish, shrimp, and lobster. Five-hundred seafood samples were collected and cultured for isolation of A. baumannii. A. baumannii isolates were identified by biochemical tests and further confirmed by the PCR. The antimicrobial resistance of isolates was studied using disk diffusion test. Twenty-eight out of 500 (5.6%) seafood samples were contaminated with A. baumannii. Fish had the highest prevalence of A. baumannii (10%), while lobster had the lowest (2.5%). A. baumannii isolates harbored the highest incidence of resistance toward tetracycline (75%), gentamicin (71.4%), ciprofloxacin (64.2%), trimethoprim (57.1%), streptomycin (53.5%), and erythromycin (50%) antimicrobial agents. The lowest incidence of resistance was obtained against chloramphenicol (3.5%) and imipenem (7.1%) antimicrobial agents. This is the first report of isolation and identification and antimicrobial resistance pattern of A. baumannii in seafood samples globally. The role of seafood samples as reservoirs of antimicrobial-resistant A. baumannii was determined. Complete cooking of seafood and prevention from their consumption in raw form can diminish the risk of A. baumannii foodborne diseases.

Using Machine Learning to Predict Antimicrobial Resistance of Acinetobacter Baumannii, Klebsiella Pneumoniae and Pseudomonas Aeruginosa Strains.

Hospital-acquired infections, particularly in ICU, are becoming more frequent in recent years, with the most serious of them being Gram-negative bacterial infections. Among them, Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa are considered the most resistant bacteria encountered in ICU and other wards. Given the fact that about 24 hours are usually required to perform common antibiotic resistance tests after the bacteria identification, the use of machine learning techniques could be an additional decision support tool in selecting empirical antibiotic treatment based on the sample type, bacteria, and patient's basic characteristics. In this article, five machine learning (ML) models were evaluated to predict antimicrobial resistance of Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. We suggest implementing ML techniques to forecast antibiotic resistance using data from the clinical microbiology laboratory, available in the Laboratory Information System (LIS).

Immunoprotectivity of Valine–glycine repeat protein G, a potent mediator of pathogenicity, against Acinetobacter baumannii

Type VI Secretion System (T6SS) contributes to both virulence and antimicrobial resistance in Acinetobacter baumannii. Valine–glycine repeat protein G (VgrG) is the core component of T6SS that exists in many bacterial pathogens that have emerged as a potent mediator of pathogenicity in A. baumannii. Two conserved sequences of vgrG 1263-2295 and vgrG1263-1608 were identified antigenic in various strains of Acinetobacter baumannii. The vgrg1263-1608 sequence was implanted in the Loopless C lobe (LCL) from N. meningitidis for surface display and exposure to functional epitopes. The VgrG and LCL-VgrG were expressed and purified. Groups of BALB/c mice were immunized with these proteins and challenged with A. baumannii. Specific IgG titers, whole-cell ELISA, animal survival rates in active and passive immunizations, the bacterial burden in mice tissues, and cytotoxicity of the proteins were determined. The specific IgG suppressed bacterial burdens in the organs, and increased survival rates were noted in the immunized mice. LCL-VgrG immunization provided better protection against A. baumannii infection than the VgrG immunization. The conserved region of VgrG is probably a safe immunogen to effective vaccine development or an antiserum to control A. baumannii infections.

Relationships between Relative Expression of RND Efflux Pump Genes, H33342 Efflux Activity, Biofilm-Forming Activity, and Antimicrobial Resistance in Acinetobacter baumannii Clinical Isolates.

Various mechanisms underlying antimicrobial resistance in Acinetobacter baumannii have been reported. However, the relationships between efflux pump activity, biofilm formation, and antimicrobial resistance in A. baumannii is controversial. In this study, we investigated the relative expression of RND efflux pump genes, H33342 efflux activity, and biofilm-forming activity in 120 A. baumannii clinical isolates, examined their potential relationships with each other, and statistically analyzed their effects on antibiotic resistance. High adeB expression and high H33342 efflux activity were correlated with low biofilm-forming activity. High adeB expression was significantly correlated with resistance to tigecycline and cefotaxime, but not with the multidrug resistance (MDR) phenotype. Importantly, only high adeJ expression was significantly correlated with the MDR phenotype and was correlated with resistance to various antibiotics. However, we found no significant correlation between adeJ expression and biofilm-forming activity. Furthermore, adeG expression was not correlated with antibiotic resistance and biofilm-forming activity. The results of multivariate analysis showed that adeB overexpression and high H33342 efflux activity were related to biofilm-forming activity, and only adeJ overexpression was significantly associated with the MDR phenotype, highlighting the importance of adeJ overexpression.

Epigallocatechin-3-gallate reduces liver and immune system damage in Acinetobacter baumannii-loaded mice with restraint stress

AimDue to the significant increase in the antimicrobial resistance of Acinetobacter baumannii (A. baumannii), new drugs to block the progression of infection are strongly needed. Epigallocatechin-3-gallate (EGCG), a major component of green tea, has exhibited potential activity against A. baumannii in vitro. The aim of this study was to determine if EGCG could be used for pretreating stress-related effects, liver damage, and immune dysfunction caused by A. baumannii infection in vivo. MethodsLevels of stress hormones, oxidative stress, liver damage, and immune components were analyzed in a murine infection model in which the mice were pretreated with EGCG for one week then intranasally inoculated with A. baumannii. The mice were restrained for 12 h to promote infection because A. baumannii is an opportunistic pathogen. The pretreatment efficacy of EGCG against A. baumannii in mice was assessed for 24 h after the bacterial infection. ResultsRestraint stress strengthened the damage from the A. baumannii infection. Pretreatment with EGCG in the murine pneumonia model markedly reduced stress hormones, oxidative metabolites, and proinflammatory cytokine production. EGCG also increased the immune function by increasing the levels of sIgA, T cells and neutrophils after infection. Moreover, pretreatment with EGCG significantly decreased the liver damage by inhibiting the levels of transaminases, oxidative stress metabolites, and cytokines, while maintaining the normal activity of CYP450 enzymes in the liver. ConclusionEGCG was efficacious as a preventative treatment for the damage seen in an experimental model of A. baumannii infection.

Antimicrobial resistance of acinetobacter baumannii infection of lower respiratory tract and mortality – A cross-sectional study from a tertiary care teaching hospital in Kerala

Background: Acinetobacter baumannii has evolved as a common Multi Drug Resistant (MDR) microbe. This study was conducted to find the profile of antimicrobial resistance and mortality and their associated factors in A. baumannii infection of lower respiratory tract. Materials and Methods: This was a record based cross sectional study done in a tertiary care teaching hospital in Kerala. Records of all the 63, A. baumannii lower respiratory infection in 2017, were retrieved and analyzed. MDR was defined as resistance to at least one agent of three or more antimicrobial classes. Proportion of MDR, carbapenam resistance and resistance to other major antimicrobials were calculated. Determinants of carbapenam resistance and its associated antimicrobial resistance were explored. Proportion of mortality and the associated factors were explored. Student’s t-test, chi-square test or fisher exact test were used appropriately. Results: Proportions of MDR and carbapenam resistance were 85.7% and 41.3% respectively. Highest proportion (90.5%) was resistant to piperazillin-tazobactam. Carbapenam resistance was associated with MDR (p-value95% CI: 63.9% to 85.3%). Older age and ICU stay prior to infection were associated with mortality (p-value Conclusions: Rates of antimicrobial resistance in Acinetobacter baumannii and the mortality were high in the setting, comparable to reports from other parts of India. The drug resistance increases hospital care burden. There is an urgent need to implement stringent infection control measures. Keywords: Acinetobacter baumannii; Nosocomial infection; Antimicrobial resistance; Multi Drug Resistance; ESKAPE.

In Vitro Evaluation of Antimicrobial Peptide Tridecaptin M in Combination with Other Antibiotics against Multidrug Resistant Acinetobacter baumannii.

The rapid emergence of antimicrobial resistance in Acinetobacter baumannii coupled with the dried pipeline of novel treatments has driven the search for new therapeutic modalities. Gram-negative bacteria have an extra outer membrane that serves as a permeability barrier for various hydrophobic and/or large compounds. One of the popular approaches to tackle this penetration barrier is use of potentiators or adjuvants in combination with traditional antibiotics. This study reports the in vitro potential of an antimicrobial peptide tridecaptin M in combination with other antibiotics against different strains of A. baumannii. Tridecaptin M sensitized the bacteria to rifampicin, vancomycin, and ceftazidime. Further, we observed that a tridecaptin M and rifampicin combination killed the bacteria completely in 4 h in an ex vivo blood infection model and was superior to rifampicin monotherapy. The study also found that concomitant administration of both compounds is not necessary to achieve the antimicrobial effect. Bacteria pre-treated with tridecaptin M (for 2–4 h) followed by exposure to rifampicin showed similar killing as obtained for combined treatment. Additionally, this combination hampered the survival of persister development in comparison to rifampicin alone. These findings encourage the future investigation of this combination to treat severe infections caused by extremely drug-resistant A. baumannii.

Effects of different resistance mechanisms on antimicrobial resistance in Acinetobacter baumannii: a strategic system for screening and activity testing of new antibiotics

A total of 50 engineered strains with various antimicrobial resistance mechanisms were constructed by in-frame deletion, site-directed mutagenesis and plasmid transformation from two fully-susceptible strains (Acinetobacter baumannii KAB1544 and ATCC 17978), including 31 strains with chromosomally-mediated resistance and 19 with plasmid-mediated resistance. Each of the 50 resistance mechanisms showed similar effects on the minimum inhibitory concentrations (MICs) of KAB1544 and ATCC 17978. Compared with the parental strains, the engineered strains related to some efflux pumps showed a significant (≥4-fold) difference in the MICs of β-lactams, quinolones, aminoglycosides, tetracyclines, folate pathway inhibitors and/or phenicols, whereas no significant effects on the MICs were found for the engineered strains lacking OmpA, CarO, Omp25, Omp33, OmpW or OprD. Mechanisms due to GyrA/ParC mutations, β-lactamases, aminoglycoside-modifying enzymes, 16S rRNA methylases and tet resistance genes contributed their corresponding resistance, as previously published. In conclusion, strains constructed in this study have clear resistance mechanisms and can be used to screen and assess compounds against specific resistance mechanisms for treating Acinetobacter. In addition to our previously published system for Enterobacteriaceae, the combination of these two systems could increase the coverage of bacterial types for drug assessment and facilitate the selection process of new candidates in drug development against drug-resistant superbugs.

Impact of Efflux Pump Inhibitor Carbonyl-Cyanide M-Chlorophenylhydrazone in Multidrug Resistant AcinetobacterSpecies Isolates from Sterile Body Fluids

Introduction: Antimicrobial resistance of Acinetobacter baumannii(A. baumannii) are rapidly emerging, becoming non-responsive to most of the commonly prescribed antibiotics and leaving us with few treatment options and galloping treatment costs. Aim: To study the effect of Efflux Pump Inhibitor (EPI) Carbonyl Cyanide 3-Chlorophenylhydrazone (CCCP) on Multidrug Resistance (MDR) A. baumannii isolates from different sterile body fluids. Materials and Methods: A total of 40 Acinetobacter species isolates from different sterile body fluids i.e., Cerebrospinal Fluid (CSF), ascitic fluid, pleural fluid, and peritoneal fluid were collected and identified by Matrix Assisted Laser Desorption/Ionisation-Time Of Flight (MALDI-TOF), Biomerieux, France. Minimum Inhibitory Concentration (MIC) of A. baumannii was determined by automated VITEK-2 Antimicrobial Susceptibility Testing (AST) system (Biomerieux, France). In addition, MIC of the isolates, grown on Mueller-Hinton Agar (MHA) plate with 15 μg/mL with EPI CCCP (Sigma Aldrich, US) was determined. For Tigecycline, MIC was determined by Broth Microdilution (BMD) method. Results: Out of 40 isolates, 34 (85%) were A. baumannii and 6 (15%) were Acinetobacter junii. Most of the Acinetobacter spps were MDR and only susceptible to few antibiotics. Most effective antibiotic was Tigecycline 25 (73.52%) followed by Co-trimoxazole 10 (29.41%). Similarly, Out of 40 isolates, 2 to 64 folds reductions in MIC was observed due to CCCP in 10 (25%) isolates for various antibiotics. Likewise, for Tigecycline, 2 to 4 folds reductions in MIC value (One strain changed from intermediate to sensitive) was observed by VITEK-2 AST which corroborated with reduction in MIC by BMD after addition of CCCP. Conclusion: MDR A. baumannii are spreading rapidly. There is the need to overcome the antimicrobial resistance by investigating resistance inhibiting substance that will help to restore antimicrobial susceptibility and bringing back the existing antibiotics in prescription.

Large-Scale Identification of AbaR-Type Genomic Islands in Acinetobacter baumannii Reveals Diverse Insertion Sites and Clonal Lineage-Specific Antimicrobial Resistance Gene Profiles.

AbaR-type genomic islands (AbaRs) are important elements responsible for antimicrobial resistance in Acinetobacter baumannii This study performed a large-scale identification of AbaRs to understand their distribution and compositions of antimicrobial resistance genes. We identified 2.89-kb left-end and 1.87-kb right-end conserved sequences (CSs) and developed a bioinformatics approach to identify AbaRs, using the CSs as signatures, in 3,148 publicly available genomes. AbaRs were prevalent in A. baumannii, being found in 2,091 genomes. They were sparse in other Acinetobacter species and confined only to this genus. Results from 111 complete genomes showed that over 85% of AbaRs resided on chromosomes. The external flanks adjacent to the inverted repeats available in all identified CSs were mapped to an AbaR-free chromosome or searched in the NCBI database for empty loci to define insertion sites. Surprisingly, 84 insertion sites with diverse origins were revealed, including 51 scattered on the chromosome, 20 plasmid borne, 12 located on prophages, transposons, ISAba1, complex AbaRs, and genomic islands of other types, and one uncharacterized, and some were strongly associated with clonal lineages. Finally, we found 994 antimicrobial resistance genes covering 28 unique genes from 70.9% (299/422) of intact AbaRs currently available. The resistance gene profiles displayed an apparent clonal lineage-specific pattern, highlighting the distinct features of AbaRs in global clone 1 (GC1) and GC2. The tet(B) gene was highly specific to the AbaRs in GC2. In conclusion, AbaRs have diverse insertion sites on the chromosome and mobile genetic elements (MGEs) and display distinct antimicrobial resistance gene profiles in different clonal lineages.

Molecular characterization and clonal dynamics of nosocomial blaOXA-23 producing XDR Acinetobacter baumannii.

The emergence of infections associated to new antimicrobial resistance in Acinetobacter baumannii (Ab) genotypes represents a major challenge. In this context, this study aimed to determine the diversity of resistance mechanisms and investigate clonal dissemination and predominant sequence types (STs) in multidrug-resistant Ab strains of clinical (tracheal aspirate, n = 17) and environmental (surface, n = 6) origins. Additionally, the major clones found in clinical (A) and environmental (H) strains had their complete genomes sequenced. All strains were submitted to polymerase chain reactions (PCR) for the detection of the ISAba1/blaOXA-51-like and ISAba1/blaOXA-23-like genes, while the expression of genes encoding the carO porin, AdeABC (adeB), AdeFGH (adeG), and AdeIJK (adeJ) efflux pumps was determined by real time PCR (qPCR). Most of the strains were characterized as extensively drug-resistant (XDR) with high minimal inhibitory concentrations (MICs) detected for tigecycline and carbapenems. Associations between ISAba1/OXA-51 and ISAba1/OXA-23 were observed in 91.3% and 52.2% of the strains, respectively. Only the adeB gene was considered hyper-expressed. Furthermore, most of the strains analyzed by the MuLtilocus Sequence-Typing (MLST) were found to belong to the clonal complex 113 (CC113). In addition, a new ST, ST1399, belonging to CC229, was also discovered herein. Strains analyzed by whole genome sequencing presented resistance genes linked to multidrug-resistance phenotypes and confirmed the presence of Tn2008, which provides high levels carbapenem-resistance.

Molecular mechanisms of antimicrobial resistance in Acinetobacter baumannii, with a special focus on its epidemiology in Lebanon.

Acinetobacter baumannii is an opportunistic bacterium involved in several types of infection with high mortality and morbidity, especially in intensive care units. Treatment of these infections remains a challenge due to the worldwide emergence of broad-spectrum resistance to many antibiotics. Following the implementation of molecular techniques to study A. baumannii outbreaks, it has been shown that they are mainly caused by specific clones such as international clones I, II and III. The present work aims to review the available data on the mechanisms underlying antimicrobial resistance in A. baumannii, with a special focus on the molecular epidemiology of this species in Lebanon.