The antimicrobial resistance landscape of Neisseria gonorrhoeae in New Zealand from November 2018 to March 2019 and the role of sexual orientation in transmission

The increasing use of culture independent diagnostic testing for the diagnosis of Neisseria gonorrhoeae infection has led to gaps in surveillance of antimicrobial resistance (AMR) rates due to limited availability of cultures. Our study reports the findings of a second national survey of N. gonorrhoeae in New Zealand, utilizing whole-genome sequencing (WGS) to study the population structure, prevalence of AMR, epidemiology and transmission of gonorrhoea isolates. We analysed 314 isolates and found a strong correlation between carriage of acquired resistance genes or chromosomal point mutations and phenotypic susceptibility testing results. Overall, the New Zealand rates of azithromycin resistance and decreased susceptibility to ceftriaxone remain lower than in most countries, which are part of the World Health Organization (WHO) Global Gonococcal Antimicrobial Surveillance Programme (GASP). The phylogeny provides evidence of a diverse population significantly associated with sexual behaviour groups. Transmission clustering with a ten single nucleotide polymorphism (SNP) cut-off identified 49 clusters, of which ten were solely associated with men who have sex with men (MSM), whereas remaining clusters included heterosexual patients, as well as MSM, suggesting that bridging of sexual networks is occurring. Utilizing pairwise SNP differences between isolates of the same sequence types we determined genetic variation for the three typing schemes used in this study [Multi locus sequence typing (MLST), multi-antigen sequence typing (NG-MAST), and sequence typing for antimicrobial resistance (NG-STAR)]. A median of 0.0 to 52.5 pairwise SNP differences within a single NG-STAR sequence type underlines previous findings of the superiority of the NG-STAR typing scheme in terms of genomic inherency. With our analysis incorporating epidemiological and genomic data, we were able to show a comprehensive overview of the N. gonorrhoeae population circulating in New Zealand, focussing on AMR and transmission within sexual networks. Regular surveillance studies to understand the origin, evolution and spread of AMR for gonorrhoea remain necessary to make informed decisions about public health guidelines, as the internationally rising rates of ceftriaxone and azithromycin resistance have already led to adaptation of current treatment guidelines in the UK and the USA, highlighting the importance of regular surveillance in individual countries.

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Neisseria gonorrhoeae clustering to reveal major European whole-genome-sequencing-based genogroups in association with antimicrobial resistance

Microbial Genomics ◽

10.1099/mgen.0.000481 ◽

2020 ◽

Author(s):

Miguel Pinto ◽

Vítor Borges ◽

Joana Isidro ◽

João Carlos Rodrigues ◽

Luís Vieira ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Type Species ◽

Transmitted Disease ◽

Epidemiological Surveillance ◽

Whole Genome ◽

Content Type ◽

Link Type

Neisseria gonorrhoeae , the bacterium responsible for the sexually transmitted disease gonorrhoea, has shown an extraordinary ability to develop antimicrobial resistance (AMR) to multiple classes of antimicrobials. With no available vaccine, managing N. gonorrhoeae infections demands effective preventive measures, antibiotic treatment and epidemiological surveillance. The latter two are progressively being supported by the generation of whole-genome sequencing (WGS) data on behalf of national and international surveillance programmes. In this context, this study aims to perform N. gonorrhoeae clustering into genogroups based on WGS data, for enhanced prospective laboratory surveillance. Particularly, it aims to identify the major circulating WGS-genogroups in Europe and to establish a relationship between these and AMR. Ultimately, it enriches public databases by contributing with WGS data from Portuguese isolates spanning 15 years of surveillance. A total of 3791 carefully inspected N. gonorrhoeae genomes from isolates collected across Europe were analysed using a gene-by-gene approach (i.e. using cgMLST). Analysis of cluster composition and stability allowed the classification of isolates into a two-step hierarchical genogroup level determined by two allelic distance thresholds revealing cluster stability. Genogroup clustering in general agreed with available N. gonorrhoeae typing methods [i.e. MLST (multilocus sequence typing), NG-MAST ( N. gonorrhoeae multi-antigen sequence typing) and PubMLST core-genome groups], highlighting the predominant genogroups circulating in Europe, and revealed that the vast majority of the genogroups present a dominant AMR profile. Additionally, a non-static gene-by-gene approach combined with a more discriminatory threshold for potential epidemiological linkage enabled us to match data with previous reports on outbreaks or transmission chains. In conclusion, this genogroup assignment allows a comprehensive analysis of N. gonorrhoeae genetic diversity and the identification of the WGS-based genogroups circulating in Europe, while facilitating the assessment (and continuous monitoring) of their frequency, geographical dispersion and potential association with specific AMR signatures. This strategy may benefit public-health actions through the prioritization of genogroups to be controlled, the identification of emerging resistance carriage, and the potential facilitation of data sharing and communication.

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Cell-free supernatants produced by lactic acid bacteria reduce Salmonella population in vitro

Microbiology ◽

10.1099/mic.0.001102 ◽

2021 ◽

Vol 167 (11) ◽

Author(s):

Alberto Gonçalves Evangelista ◽

Jessica Audrey Feijó Corrêa ◽

João Vitor Garcia dos Santos ◽

Eduardo Henrique Custódio Matté ◽

Mônica Moura Milek ◽

...

Keyword(s):

Antimicrobial Activity ◽

Lactic Acid ◽

Antimicrobial Resistance ◽

Lactic Acid Bacteria ◽

Type Species ◽

Feed Additives ◽

Poultry Feed ◽

Content Type ◽

Link Type

The genus Salmonella is closely associated with foodborne outbreaks and animal diseases, and reports of antimicrobial resistance in Salmonella species are frequent. Several alternatives have been developed to control this pathogen, such as cell-free supernatants (CFS). Our objective here was to evaluate the use of lactic acid bacteria (LAB) CFS against Salmonella in vitro. Seventeen strains of LAB were used to produce CFS, and their antimicrobial activity was screened towards six strains of Salmonella . In addition, CFS were also pH-neutralized and/or boiled. Those with the best results were lyophilized. MICs of lyophilized CFS were 11.25–22.5 g l–1. Freeze-dried CFS were also used to supplement swine and poultry feed (11.25 g kg–1) and in vitro simulated digestion of both species was performed, with Salmonella contamination of 5×106 and 2×105 c.f.u. g−1 of swine and poultry feed, respectively. In the antimicrobial screening, all acidic CFS were able to inhibit the growth of Salmonella . After pH neutralization, Lactobacillus acidophilus Llorente, Limosilactobacillus fermentum CCT 1629, Lactiplantibacillus plantarum PUCPR44, Limosilactobacillus reuteri BioGaia, Lacticaseibacillus rhamnosus ATCC 7469 and Pediococcus pentosaceus UM116 CFS were the only strains that partially maintained their antimicrobial activity and, therefore, were chosen for lyophilization. In the simulated swine digestion, Salmonella counts were reduced ≥1.78 log c.f.u. g–1 in the digesta containing either of the CFS. In the chicken simulation, a significant reduction was obtained with all CFS used (average reduction of 0.59±0.01 log c.f.u. ml–1). In general, the lyophilized CFS of L. fermentum CCT 1629, L. rhamnosus ATCC 7469 and L. acidophilus Llorente presented better antimicrobial activity. In conclusion, CFS show potential as feed additives to control Salmonella in animal production and may be an alternative to the use of antibiotics, minimizing problems related to antimicrobial resistance.

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Comparative genomics of Staphylococcus epidermidis from prosthetic-joint infections and nares highlights genetic traits associated with antimicrobial resistance, not virulence

Microbial Genomics ◽

10.1099/mgen.0.000504 ◽

2021 ◽

Cited By ~ 1

Author(s):

Emeli Månsson ◽

Thor Bech Johannesen ◽

Åsa Nilsdotter-Augustinsson ◽

Bo Söderquist ◽

Marc Stegger

Keyword(s):

Population Structure ◽

Antimicrobial Resistance ◽

Staphylococcus Epidermidis ◽

Type Species ◽

Genetic Traits ◽

Content Type ◽

Link Type ◽

Joint Infections ◽

Prosthetic Joint ◽

Prosthetic Joint Infections

There is increased awareness of the worldwide spread of specific epidemic multidrug-resistant (MDR) lineages of the human commensal Staphylococcus epidermidis . Here, using bioinformatic analyses accounting for population structure, we determined genomic traits (genes, SNPs and k-mers) that distinguish S. epidermidis causing prosthetic-joint infections (PJIs) from commensal isolates from nares, by analysing whole-genome sequencing data from S. epidermidis from PJIs prospectively collected over 10 years in Sweden, and contemporary S. epidermidis from the nares of patients scheduled for arthroplasty surgery. Previously suggested virulence determinants and the presence of genes and mutations linked to antimicrobial resistance (AMR) were also investigated. Publicly available S. epidermidis sequences were used for international extrapolation and validation of findings. Our data show that S. epidermidis causing PJIs differed from nasal isolates not by virulence but by traits associated with resistance to compounds used in prevention of PJIs: β-lactams, aminoglycosides and chlorhexidine. Almost a quarter of the PJI isolates did not belong to any of the previously described major nosocomial lineages, but the AMR-related traits were also over-represented in these isolates, as well as in international S. epidermidis isolates originating from PJIs. Genes previously associated with virulence in S. epidermidis were over-represented in individual lineages, but failed to reach statistical significance when adjusted for population structure. Our findings suggest that the current strategies for prevention of PJIs select for nosocomial MDR S. epidermidis lineages that have arisen from horizontal gene transfer of AMR-related traits into multiple genetic backgrounds.

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Emergence of mgrB locus deletion mediating polymyxin resistance in pandemic KPC-producing Klebsiella pneumoniae ST15 lineage

Journal of Medical Microbiology ◽

10.1099/jmm.0.001309 ◽

2021 ◽

Author(s):

Luís Guilherme de Araújo Longo ◽

Herrison Fontana ◽

Viviane Santos de Sousa ◽

Natalia Chilinque Zambão da Silva ◽

Ianick Souto Martins ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Klebsiella Pneumoniae ◽

Type Species ◽

Virulence Genes ◽

Health Concern ◽

Beta Lactamase ◽

Content Type ◽

Link Type ◽

Antimicrobial Resistance Genes ◽

Encoding Gene

Klebsiella pneumoniae causes a diversity of infections in both healthcare and community settings. This pathogen is showing an increased ability to accumulate antimicrobial resistance and virulence genes, making it a public health concern. Here we describe the whole-genome sequence characteristics of an ST15 colistin-resistant K. pneumoniae isolate obtained from a blood culture of a 79-year-old female patient admitted to a university hospital in Brazil. Kp14U04 was resistant to most clinically useful antimicrobial agents, remaining susceptible only to aminoglycosides and fosfomycin. The colistin resistance in this isolate was due to a ~1.3 kb deletion containing four genes, namely mgrB, yebO, yobH and the transcriptional regulator kdgR. The study isolate presented a variety of antimicrobial resistance genes, including the carbapenemase-encoding gene bla KPC-2, the extended-spectrum beta-lactamase (ESBL)-encoding gene bla SHV-28 and the beta-lactamase-encoding gene bla OXA-1. Additionally, Kp14U04 harboured a multiple stress resistance protein, efflux systems and regulators, heavy metal resistance and virulence genes, plasmids, prophage-related sequences and genomic islands. These features revealed the high potential of this isolate to resist antimicrobial therapy, survive in adverse environments, cause infections and overcome host defence mechanisms.

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Evaluation of WGS performance for bacterial pathogen characterization with the Illumina technology optimized for time-critical situations

Microbial Genomics ◽

10.1099/mgen.0.000699 ◽

2021 ◽

Vol 7 (11) ◽

Author(s):

Bert Bogaerts ◽

Raf Winand ◽

Julien Van Braekel ◽

Stefan Hoffman ◽

Nancy H. C. Roosens ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Type Species ◽

Bacterial Pathogen ◽

Read Length ◽

Time Data ◽

Content Type ◽

Emergency Situations ◽

Link Type ◽

Pathogen Characterization ◽

Time Critical

Whole genome sequencing (WGS) has become the reference standard for bacterial outbreak investigation and pathogen typing, providing a resolution unattainable with conventional molecular methods. Data generated with Illumina sequencers can however only be analysed after the sequencing run has finished, thereby losing valuable time during emergency situations. We evaluated both the effect of decreasing overall run time, and also a protocol to transfer and convert intermediary files generated by Illumina sequencers enabling real-time data analysis for multiple samples part of the same ongoing sequencing run, as soon as the forward reads have been sequenced. To facilitate implementation for laboratories operating under strict quality systems, extensive validation of several bioinformatics assays (16S rRNA species confirmation, gene detection against virulence factor and antimicrobial resistance databases, SNP-based antimicrobial resistance detection, serotype determination, and core genome multilocus sequence typing) for three bacterial pathogens ( Mycobacterium tuberculosis , Neisseria meningitidis , and Shiga-toxin producing Escherichia coli ) was performed by evaluating performance in function of the two most critical sequencing parameters, i.e. read length and coverage. For the majority of evaluated bioinformatics assays, actionable results could be obtained between 14 and 22 h of sequencing, decreasing the overall sequencing-to-results time by more than half. This study aids in reducing the turn-around time of WGS analysis by facilitating a faster response in time-critical scenarios and provides recommendations for time-optimized WGS with respect to required read length and coverage to achieve a minimum level of performance for the considered bioinformatics assay(s), which can also be used to maximize the cost-effectiveness of routine surveillance sequencing when response time is not essential.

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Genomic surveillance of Escherichia coli and Klebsiella spp. in hospital sink drains and patients

Microbial Genomics ◽

10.1099/mgen.0.000391 ◽

2020 ◽

Vol 6 (7) ◽

Author(s):

Bede Constantinides ◽

Kevin K. Chau ◽

T. Phuong Quan ◽

Gillian Rodger ◽

Monique I. Andersson ◽

...

Keyword(s):

Escherichia Coli ◽

Antimicrobial Resistance ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Type Species ◽

Whole Genome ◽

Content Type ◽

E Coli ◽

Link Type ◽

Antimicrobial Resistance Genes

Escherichia coli and Klebsiella spp. are important human pathogens that cause a wide spectrum of clinical disease. In healthcare settings, sinks and other wastewater sites have been shown to be reservoirs of antimicrobial-resistant E. coli and Klebsiella spp., particularly in the context of outbreaks of resistant strains amongst patients. Without focusing exclusively on resistance markers or a clinical outbreak, we demonstrate that many hospital sink drains are abundantly and persistently colonized with diverse populations of E. coli , Klebsiella pneumoniae and Klebsiella oxytoca , including both antimicrobial-resistant and susceptible strains. Using whole-genome sequencing of 439 isolates, we show that environmental bacterial populations are largely structured by ward and sink, with only a handful of lineages, such as E. coli ST635, being widely distributed, suggesting different prevailing ecologies, which may vary as a result of different inputs and selection pressures. Whole-genome sequencing of 46 contemporaneous patient isolates identified one (2 %; 95 % CI 0.05–11 %) E. coli urine infection-associated isolate with high similarity to a prior sink isolate, suggesting that sinks may contribute to up to 10 % of infections caused by these organisms in patients on the ward over the same timeframe. Using metagenomics from 20 sink-timepoints, we show that sinks also harbour many clinically relevant antimicrobial resistance genes including bla CTX-M, bla SHV and mcr, and may act as niches for the exchange and amplification of these genes. Our study reinforces the potential role of sinks in contributing to Enterobacterales infection and antimicrobial resistance in hospital patients, something that could be amenable to intervention. This article contains data hosted by Microreact.

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Isolation and characterization of bacteria from activated sludge capable of degrading 17α-ethinylestradiol, a contaminant of high environmental concern

Microbiology ◽

10.1099/mic.0.001038 ◽

2021 ◽

Vol 167 (4) ◽

Author(s):

Tânia Luz Palma ◽

Anastasiia Shylova ◽

Maria Clara Costa

Keyword(s):

Type Species ◽

Wastewater Treatment Plants ◽

Environmental Concern ◽

Degradation Products ◽

Tca Cycle ◽

Pantoea Agglomerans ◽

World Health ◽

Content Type ◽

Link Type ◽

Isolation And Characterization

The compound 17α-ethinylestradiol (EE2) is a synthetic oestrogen which is classified as a group 1 carcinogen by the World Health Organization. Together with other endocrine disruptor compounds, EE2 has been included in the surface water Watch List by the European Commission, since it causes severe adverse effects in ecosystems. Thus, it became a high priority to find or improve processes such as biodegradation of EE2 to completely remove this drug from the wastewater treatment plants (WWTPs). The present study aimed at the isolation of bacteria capable of degrading EE2 using environmental samples, namely a sludge from the Faro Northwest WWTP. Four isolates with ability to grow in the presence of 50 mg l−1 EE2 were obtained. The analysis of 16SrRNA gene sequences identified the isolated bacteria as Acinetobacter bouvetii, Acinetobacter kookii, Pantoea agglomerans and Shinella zoogloeoides . The results of biodegradation assays showed that Acinetobacter bouvetii , Acinetobacter kookii , Pantoea agglomerans and Shinella zoogloeoides were able to degrade 47±4 %, 55±3 %, 64±4% and 35±4 %, respectively of 13 mg l−1 EE2 after 168 h at 28 °C. To the best of our knowledge, these bacterial isolates were identified as EE2 degraders for the first time. In a preliminary experiment on the identification of metabolic products resulting from EE2 degradation products such as estrone (E1), γ-lactone compounds, 2-pentanedioic acid and 2-butenedioic acid an intermediate metabolite of the TCA cycle, were detected.

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Comparative study of multidrug-resistant Enterococcus faecium obtained from different hosts

Journal of Medical Microbiology ◽

10.1099/jmm.0.001340 ◽

2021 ◽

Author(s):

Aleksandra Trościańczyk ◽

Aneta Nowakiewicz ◽

Sebastian Gnat ◽

Dominik Łagowski ◽

Marcelina Osińska ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Resistance Genes ◽

Host Species ◽

Enterococcus Faecium ◽

Type Species ◽

Animal Species ◽

Multidrug Resistant ◽

Content Type ◽

Link Type ◽

High Level

Introduction. The possible transfer of antimicrobial resistance genes between Enterococcus faecium isolates from humans and different animal species, including those not covered by monitoring programs (e.g. pet and wildlife), poses a serious threat to public health. Hypothesis/Gap Statement. Little is known about occurrence and mechanisms of phenomenon of multidrug resistance of E. faecium isolated from various host species in Poland. Aim. The aim of the study was to characterize multidrug-resistant E. faecium isolated from humans and animals (livestock, pets and wildlife) in terms of the occurrence of genetic markers determining resistance. Methodology. Bacterial isolates were tested for phenotypic resistance and the presence of genes encoding resistance to macrolides, tetracycline, aminoglycosides, aminocyclitols and phenicols as well as efflux pump (emeA), resolvase (tndX) and integrase (Int-Tn) genes. The quinolone resistance-determining regions of gyrA and parC were sequenced. Results. Human isolates of E. faecium were characterized by high-level resistance to: ciprofloxacin, enrofloxacin, erythromycin (100 %), as well, as aminoglycosides resistance (kanamycin – 100%, streptomycin – 78 %, gentamicin – 78%). Regardless of the animal species, high level of resistance of E. faecium to tetracycline (from 88–100 %), erythromycin (from 82–94 %) and kanamycin (from 36–100 %) was observed. All E. faecium isolates from wildlife were resistant to fluoroquinolones. However, full susceptibility to vancomycin was observed in all isolates tested. Phenotypic antimicrobial resistance of E. faecium was identified in the presence of the following resistance genes: erm(B) (70%), msr(A) (50 %), tet(L) (35 %), tet(K) (34 %), tet(M) (76 %), aac(6’)-Ie-aph(2″)-Ia (25%), ant(6)-Ia (31%), aph(3)-IIIa (68 %), (tndX) (23 %), and integrase gene (Int-Tn) (34 %). A correlation between an amino acid substitution at positions 83 and 87 of gyrA and position 80 of parC and the high-level fluoroquinolone resistance in E. faecium has been observed as well. Conclusion. The level and range of antimicrobial resistance and the panel of resistance determinants is comparable between E. faecium isolates, despite host species.

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Antimicrobial resistance prevalence in commensal Escherichia coli from broilers, fattening turkeys, fattening pigs and veal calves in European countries and association with antimicrobial usage at country level

Journal of Medical Microbiology ◽

10.1099/jmm.0.001176 ◽

2020 ◽

Vol 69 (4) ◽

pp. 537-547 ◽

Cited By ~ 3

Author(s):

Daniela Ceccarelli ◽

Ayla Hesp ◽

Jeanet van der Goot ◽

Philip Joosten ◽

Steven Sarrazin ◽

...

Keyword(s):

Escherichia Coli ◽

Antimicrobial Resistance ◽

Type Species ◽

European Countries ◽

Content Type ◽

E Coli ◽

Veal Calves ◽

Link Type ◽

Country Level ◽

Fattening Pigs

The aim of this article is to report on antimicrobial resistance (AMR) in commensal Escherichia coli from livestock from several European countries. The relationships with antimicrobial usage (AMU) at country level and harmonized indicators to cover the most relevant AMR aspects for human health in animal production were also investigated. E. coli were isolated in faeces from broilers and fattening pigs (from nine countries), and fattening turkeys and veal calves (from three countries) and screened against a fixed antimicrobial panel. AMU data were collected at farm and average treatment incidences stratified by antimicrobial class, country and livestock species were calculated. Associations between AMR and AMU at country level were analysed. Independent of animal species, the highest resistance was observed for ampicillin, sulphamethoxazole, tetracycline and trimethoprim. E. coli from broilers showed the highest resistance level for (fluoro)quinolones, and multidrug resistance peaked in broilers and fattening turkeys. Colistin resistance was observed at very low levels with the exception of fattening turkeys. High resistance to third- and fourth-generation cephalosporins was detected in broilers and fattening turkeys. The lowest levels of resistance were for meropenem, azithromycin and tigecycline (<1 %). Significant correlations between resistance and usage at country level were detected in broilers for polymyxins and aminoglycosides, and in fattening pigs for cephalosporins, amphenicols, fluoroquinolones and polymyxins. None of the correlations observed between AMR and AMU were statistically significant for fattening turkey and veal calves. The strength of the analysis performed here is the correlation of aggregated data from the same farms at country level for both AMU and AMR within antimicrobial classes.

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Molecular docking, dynamics and free energy analyses of Acinetobacter baumannii OXA class enzymes with carbapenems investigating their hydrolytic mechanisms

Journal of Medical Microbiology ◽

10.1099/jmm.0.001233 ◽

2020 ◽

Vol 69 (8) ◽

pp. 1062-1078

Author(s):

Balajee Ramachandran ◽

Jeyaraman Jeyakanthan ◽

Bruno S. Lopes

Keyword(s):

Free Energy ◽

Acinetobacter Baumannii ◽

Type Species ◽

Three Dimensional ◽

World Health ◽

Phenotypic Data ◽

Content Type ◽

Beta Lactamases ◽

Link Type ◽

Class D

Introduction. Acinetobacter baumannii is a critical priority pathogen listed by the World Health Organization due to increasing levels of resistance to carbapenem classes of antibiotics. It causes wound and other nosocomial infections, which can be life-threatening. Hence, there is an urgent need for the development of new classes of antibiotics. Aim. To study the interaction of carabapenems with class D beta-lactamases (oxacillinases) and analyse drug resistance by studying enzyme–substrate complexes using modelling approaches as a means of establishing correlations with the phenotypic data. Methodology. The three-dimensional structures of carbapenems (doripenem, ertapenem, imipenem and meropenem) were obtained from DrugBank and screened against class D beta-lactamases. Further, the study was extended with their variants. The variants’ structure was homology-modelled using the Schrödinger Prime module (Schrödinger LLC, NY, USA). Results. The first discovered intrinsic beta-lactamase of Acinetobacter baumannii , OXA-51, had a binding energy value of −40.984 kcal mol−1, whereas other OXA-51 variants, such as OXA-64, OXA-110 and OXA-111, have values of −60.638, –66.756 and −67.751 kcal mol−1, respectively. The free energy values of OXA-51 variants produced better results than those of other groups. Conclusions. Imipenem and meropenem showed MIC values of 2 and 8 µg ml−1, respectively against OXA-51 in earlier studies, indicating that these are the most effective drugs for treatment of A. baumannii infection. According to our results, OXA-51 is an active enzyme that shows better interactions and is capable of hydrolyzing carbapenems. When correlating the hydrogen-bonding interaction with MIC values, the predicted results are in good agreement and might provide initial insights into performing similar studies related to OXA variants or other antibiotic–enzyme-based studies.

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