Antimicrobial resistance pattern and molecular epidemiology of ESBL and MBL producing Acinetobacter baumannii isolated from hospitals in Minia, Egypt

Introduction: Multidrug resistant (MDR) Acinetobacter baumanii (A. baumannii) strains have emerged as novel nosocomial pathogens threatening patients’ lives, especially in intensive-care units (ICUs). This study aims to determine the prevalence of carbapenemase genes and CTX-M-15 and the resistance pattern of carbapenemase producing isolates. Methods: A total of 530 clinical specimens were collected from patients suffering from different infections, antibiotic susceptibility test was performed using kirby-bauer disk diffusion method. ESβL production was detected phenotypically by double-disc synergy test (DDST). Carbapenemase production was tested by Modified Hodge Test (MHT). Then, these isolates were tested for MBL detection by disc potentiation test. Carbapenemase encoding genes (VIM, IMP, GIM and SPM, OXA-51, OXA-23 and OXA-143) and CTX-M-15 were tested by polymerase chain reaction (PCR). Results: Out of 530 samples, 20 bacterial isolates were identified as A. baumannii from different infectious cases, 35% of isolates were ESBL-producers. Eleven isolates were resistant to imipenem (4 isolates) and meropenem (7 isolates). All carbapenem resistant isolates were MHT positive. Nine (45%) isolates were confirmed as A. baumannii by OXA-51 (all were carbapenem resistant). Distribution of IMP, VIM, GIM and SPM, OXA-23, OXA-143 and CTX-M-15 by PCR were 55, 50, 50, 25, 35, 45 and 33% respectively. Conclusion: The high prevalence of resistance genes and the resistance pattern of the isolates indicate that the detection of ESBLs and MBLs phenotypically and genotypically with the study of the resistance pattern of the isolates is critically important for the surveillance of drug resistance in the hospital environment

Global genomic epidemiology of chromosomally mediated non-enzymatic carbapenem resistance in Acinetobacter baumannii: on the way to predict and modify resistance

IntroductionAlthough carbapenemases are frequently reported in resistant A. baumannii clinical isolates, other chromosomally mediated elements of resistance that are considered essential are frequently underestimated. Having a wide substrate range, multidrug efflux pumps frequently underlie antibiotic treatment failure. Recognizing and exploiting variations in multidrug efflux pumps and penicillin-binding proteins (PBPs) is an essential approach in new antibiotic drug discovery and engineering to meet the growing challenge of multidrug-resistant Gram-negative bacteria.MethodsA total of 980 whole genome sequences of A. baumannii were analyzed. Nucleotide sequences for the genes studied were queried against a custom database of FASTA sequences using the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) system. The correlation between different variants and carbapenem Minimum Inhibitory Concentrations (MICs) was studied. PROVEAN and I-Mutant predictor suites were used to predict the effect of the studied amino acid substitutions on protein function and protein stability. Both PsiPred and FUpred were used for domain and secondary structure prediction. Phylogenetic reconstruction was performed using SANS serif and then visualized using iTOL and Phandango.ResultsExhibiting the highest detection rate, AdeB codes for an important efflux-pump structural protein. T48V, T584I, and P660Q were important variants identified in the AdeB-predicted multidrug efflux transporter pore domains. These can act as probable targets for designing new efflux-pump inhibitors. Each of AdeC Q239L and AdeS D167N can also act as probable targets for restoring carbapenem susceptibility. Membrane proteins appear to have lower predictive potential than efflux pump-related changes. OprB and OprD changes show a greater effect than OmpA, OmpW, Omp33, and CarO changes on carbapenem susceptibility. Functional and statistical evidence make the variants T636A and S382N at PBP1a good markers for imipenem susceptibility and potential important drug targets that can modify imipenem resistance. In addition, PBP3_370, PBP1a_T636A, and PBP1a_S382N may act as potential drug targets that can be exploited to counteract imipenem resistance.ConclusionThe study presents a comprehensive epidemiologic and statistical analysis of potential membrane proteins and efflux-pump variants related to carbapenem susceptibility in A. baumannii, shedding light on their clinical utility as diagnostic markers and treatment modification targets for more focused studies of candidate elements

Tenacibaculosis caused by Tenacibaculum maritimum: Updated knowledge of this marine bacterial fish pathogen

Tenacibaculosis occurs due to the marine bacterial pathogen Tenacibaculum maritimum. This ulcerative disease causes high mortalities for various marine fish species worldwide. Several external clinical signs can arise, including mouth erosion, epidermal ulcers, fin necrosis, and tail rot. Research in the last 15 years has advanced knowledge on the traits and pathogenesis mechanisms of T. maritimum. Consequently, significant progress has been made in defining the complex host-pathogen relationship. Nevertheless, tenacibaculosis pathogenesis is not yet fully understood. Continued research is urgently needed, as demonstrated by recent reports on the re-emerging nature of tenacibaculosis in salmon farms globally. Current sanitary conditions compromise the development of effective alternatives to antibiotics, in addition to hindering potential preventive measures against tenacibaculosis. The present review compiles knowledge of T. maritimum reported after the 2006 review by Avendaño-Herrera and colleagues. Essential aspects are emphasized, including antigenic and genomic characterizations and molecular diagnostic procedures. Further summarized are the epidemiological foundations of the T. maritimum population structure and elucidations as to the virulence mechanisms of pathogenic isolates, as found using biological, microbiological, and genomic techniques. This comprehensive source of reference will undoubtable serve in tenacibaculosis prevention and control within the marine fish farming industry. Lastly, knowledge gaps and valuable research areas are indicated as potential guidance for future studies

The predictive potential of different molecular markers linked to amikacin susceptibility phenotypes in Pseudomonas aeruginosa.

Informed antibiotic prescription offers a practical solution to antibiotic resistance problem. With the increasing affordability of different sequencing technologies, molecular-based resistance prediction would direct proper antibiotic selection and preserve available agents. Amikacin is a broad-spectrum aminoglycoside exhibiting higher clinical efficacy and less resistance rates in Ps. aeruginosa due to its structural nature and its ability to achieve higher serum concentrations at lower therapeutic doses. This study examines the predictive potential of molecular markers underlying amikacin susceptibility phenotypes in order to provide improved diagnostic panels. Using a predictive model, genes and variants underlying amikacin resistance have been statistically and functionally explored in a large comprehensive and diverse set of Ps. aeruginosa completely sequenced genomes. Different genes and variants have been examined for their predictive potential and functional correlation to amikacin susceptibility phenotypes. Three predictive sets of molecular markers have been identified and can be used in a complementary manner, offering promising molecular diagnostics. armR, nalC, nalD, mexR, mexZ, ampR, rmtD, nalDSer32Asn, fusA1Y552C, fusA1D588G, arnAA170T, and arnDG206C have been identified as the best amikacin resistance predictors in Ps. aeruginosa while faoAT385A, nuoGA890T, nuoGA574T, lptAT55A, lptAR62S, pstBR87C, gidBE126G, gidBQ28K, amgSE108Q, and rplYQ41L have been identified as the best amikacin susceptibility predictors. Combining different measures of predictive performance together with further functional analysis can help design new and more informative molecular diagnostic panels. This would greatly inform and direct point of care diagnosis and prescription, which would consequently preserve amikacin functionality and usefulness

Pangenome analysis of Corynebacterium striatum: insights into a neglected multidrug-resistant pathogen

Abstract Background Over the past two decades, Corynebacterium striatum has been increasingly isolated from clinical cultures with most isolates showing increased antimicrobial resistance (AMR) to last resort agents. Advances in the field of pan genomics would facilitate the understanding of the clinical significance of such bacterial species previously thought to be among commensals paving the way for identifying new drug targets and control strategies. Methods We constructed a pan-genome using 310 genome sequences of C. striatum. Pan-genome analysis was performed using three tools including Roary, PIRATE, and PEPPAN. AMR genes and virulence factors have been studied in relation to core genome phylogeny. Genomic Islands (GIs), Integrons, and Prophage regions have been explored in detail. Results The pan-genome ranges between a total of 5253–5857 genes with 2070 − 1899 core gene clusters. Some antimicrobial resistance genes have been identified in the core genome portion, but most of them were located in the dispensable genome. In addition, some well-known virulence factors described in pathogenic Corynebacterium species were located in the dispensable genome. A total of 115 phage species have been identified with only 44 intact prophage regions. Conclusion This study presents a detailed comparative pangenome report of C. striatum. The species show a very slowly growing pangenome with relatively high number of genes in the core genome contributing to lower genomic variation. Prophage elements carrying AMR and virulence elements appear to be infrequent in the species. GIs appear to offer a prominent role in mobilizing antibiotic resistance genes in the species and integrons occur at a frequency of 50% in the species. Control strategies should be directed against virulence and resistance determinants carried on the core genome and those frequently occurring in the accessory genome

Investigating Virological, Immunological, and Pathological Avenues to Identify Potential Targets for Developing COVID-19 Treatment and Prevention Strategies

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus causing respiratory disease commonly known as COVID-19. This novel coronavirus transmits from human to human and has caused profound morbidity and mortality worldwide leading to the ongoing pandemic. Moreover, disease severity differs considerably from individual to individual. Investigating the virology of COVID-19 and immunological pathways underlying its clinical manifestations will enable the identification and design of effective vaccines and potential therapies. In this review, we explore COVID-19 virology, the contribution of the immune system (innate and adaptive) during infection and control of the virus. Finally, we highlight vaccine development and implications of immune system modulation for potential therapeutic interventions to design better therapeutic strategies to guide future cure.https://scholarworks.uaeu.ac.ae/uaeu_books/1003/thumbnail.jp

Nanomedicine as a promising therapeutic approach for COVID-19

The COVID-19 pandemic caused by the newly emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) puts the world in an unprecedented crisis, leaving behind huge human losses and deep socioeconomic damages. Due to the lack of specific treatment against SARS-CoV-2, effective vaccines and antiviral agents are urgently needed to properly restrain the COVID-19 pandemic. Repositioned drugs such as remdesivir have revealed a promising clinical efficacy against COVID-19. Interestingly, nanomedicine as a promising therapeutic approach could effectively help win the battle between coronaviruses (CoVs) and host cells. This review discusses the potential therapeutic approaches, in addition to the contribution of nanomedicine against CoVs in the fields of vaccination, diagnosis and therapy.https://scholarworks.uaeu.ac.ae/uaeu_books/1005/thumbnail.jp