Unveiling the ecological landscape of bacterial ß-lactam resistance in Delhi-national capital region, India: An emerging health concern.

Inappropriate antibiotic use not only amplifies the threat of antimicrobial resistance (AMR), moreover exacerbates the spread of resistant bacterial strains and genes in the environment, underscoring the critical need for effective research and interventions. Our aim is to assess the prevalence and resistance characteristics of ß-lactam resistant bacteria (BLRB) and ß-lactamase resistant bacterial genes (BLRBGs) under various environmental conditions within Delhi NCR, India. Using a culture-dependent method, we isolated 130 BLRB from 75 different environmental samples, including lakes, ponds, the Yamuna River, agricultural soil, aquatic weeds, drains, dumping yards, STPs, and gaushalas. Tests for antibiotic susceptibility were conducted in addition to phenotypic and genotypic identification of BLs and integron genes. The water and sediment samples recorded an average bacterial abundance of 3.6 × 106 CFU/mL and an average ampicillin-resistant bacterial count of 2.2 × 106 CFU/mL, which can be considered a potent reservoir of BLRB and BLRBGs. The majority of the BLRB discovered are opportunistic pathogens from the Bacillus, Aeromonas, Pseudomonas, Enterobacter, Escherichia, and Klebsiella genera, with Multiple Antibiotic Resistance (MAR) index ≥0.2 against a wide variety of ß-lactams and ß-lactamase (BLs) inhibitor combinations. The antibiotic resistance pattern was similar in the case of bacteria isolated from STPs. Meanwhile, bacteria isolated from other sources were diverse in their antibiotic resistance profile. Interestingly, we discovered that 10 isolates of various origins produce both Extended Spectrum BLs and Metallo BLs, as well as found harboring blaTEM, blaCTX, blaOXA, blaSHV, int-1, and int-3 genes. Enterobacter cloacae (S50/A), a common nosocomial pathogen isolated from Yamuna River sediment samples at Nizamuddin point, possesses three BLRBGs (blaTEM, blaCTX, and blaOXA) and a MAR index of 1.0, which is a major cause for concern. Therefore, identifying the source, origin and dissemination of BLRB and BLRGs in the environment is of the utmost importance for designing effective mitigation approaches to reduce a load of antimicrobial resistance factors in the environmental settings.

Computational insights into the role of structurally diverse plant secondary metabolites as inhibitors against Imidazole Glycerol Phosphate Dehydratase of Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) is one of the major causes of death worldwide and there is a pressing need for the development of novel drug leads. The Imidazole Glycerol Phosphate Dehydratase (IGPD) of Mtb is one of the key enzymes in the histidine biosynthesis pathway and has been recognized as the potentially underexploited drug target for anti-tuberculosis treatment. In the present study, 6063 structurally diverse plant secondary metabolites (PSM) were screened for their efficiency in inhibiting the catalytic activity of IGPD through molecular docking. The top 150 PSMs with the lowest binding energy represent the chemical classes, including Tannins (34%), Flavonoid Glycosides (14%), Terpene Glycosides (10%), Steroid Lactones (9.3%), Flavonoids (6.6%), Steroidal Glycosides (4.6%), etc. Bismahanine, Ashwagandhanolide, and Daurisoline form stable IGPD-inhibitor complexes with binding free energies of -291.3 ± 16.5, -279.0 ± 25.0, and -279.8 ± 17.6 KJ/mol, respectively, as determined by molecular dynamics simulations. These PSM demonstrated strong H-bond interactions with the amino acid residues Ile279, Arg281, and Lys276 in the catalytic region of IGPD, as revealed by structural snapshots. On the basis of our findings, these three PSM could be considered as possible leads against IGPD and should be explored in vitro and in vivo.Communicated by Ramaswamy H. Sarma.

Imidazole Glycerol Phosphate Dehydratase (IGPD) is an unexplored drug target in tuberculosis therapy.Inhibitory potential of 6063 plant secondary metabolites (PSM) against IGPD enzyme was studied.Ensemble docking and structural-activity relationship studies ascertained the group of diverse molecules.MD simulations predicted Bismahanine and Ashwagandhanolide as possible inhibitors of IGPD.

Computational and data mining studies to understand the distribution and dynamics of Temoneria (TEM) ß-lactamase and their interaction with ß-lactam and ß-lactamase inhibitors.

ß-lactams are large group of antibiotics widely used to suppress the bacterial growth by inhibiting cell wall synthesis. Bacterial resistance against ß-lactam antibiotics is primarily mediated through the production of Temoneria (TEM) ß-lactamase (BLs), with almost 474 variants identified in Lactamase Engineering Database (LacED). The present study aims to develop a model to track the evolution of TEM BLs and their interactions with ß-lactam and BLs inhibitors through data mining and computational approaches. Further, the model will be used to predict the effective combinations of ß-lactam and BLs inhibitors to treat the bacterial infection harbouring emerging variants of ß-lactamase. The molecular docking study results demonstrated that most TEM mutants recorded the least binding energy to penicillin and cephalosporin (I/II/III/IV/V generations) class of antibiotics. On the contrary, the same mutants recorded higher binding energy to carbapenem and Monobactam class of antibiotics. Among the BLs inhibitors, tazobactam recorded the least binding energy against most of the TEM mutants, indicating that it can lower the catalytic activity of TEM BLs, thereby potentiating antibiotic action. Similarly, data mining work has assisted us in creating a database of TEM mutants that has comprehensive data on mutations, bacterial diversity, Km, MIC, and IRT types. It has been noted that earlier released antibiotics like amoxicillin and ampicillin had lower Km and higher MIC values, which indicates the prevalence of bacterial resistance. By analysing the differential binding energy (ΔBE) of the selected TEM mutants against ß-lactam and BLs inhibitors, the most effective combination of ß-lactam (carbapenem and monobactam class of antibiotics) and BLs inhibitors (tazobactam) was identified, to cure bacterial diseases/infections and to prevent similar antibiotic resistance outbreaks. Therefore, our study opens a new avenue in developing strategies to manage antibiotic resistance in bacteria.

Audit of the Sydney Local Health District Public Health Unit notification and contact tracing system during the first wave of COVID-19.

OBJECTIVE: To conduct a real-time audit to assess a Continuous Quality Improvement (CQI) activity to improve the quality of public health data in the Sydney Local Health District (SLHD) Public Health Unit during the first wave of COVID-19. METHODS: A real-time audit of the Notifiable Conditions Information Management System was conducted for positive cases of COVID-19 and their close contacts from SLHD. After recording missing and inaccurate data, the audit team then corrected the data. Multivariable regression models were used to look for associations with workload and time. RESULTS: A total of 293 cases were audited. Variables measuring completeness were associated with improvement over time (p<0.0001), whereas those measuring accuracy reduced with increased workload (p=0.0003). In addition, the audit team achieved 100% data quality by correcting data. CONCLUSION: Utilising a team, separate from operational staff, to conduct a real-time audit of data quality is an efficient and effective way of improving epidemiological data. Implications for public health: Implementation of CQI in a public health unit can improve data quality during times of stress. Auditing teams can also act as an intervention in their own right to achieve high-quality data at minimal cost. Together, this can result in timely and high-quality public health data.

In silico studies evidenced the role of structurally diverse plant secondary metabolites in reducing SARS-CoV-2 pathogenesis.

Plants are endowed with a large pool of structurally diverse small molecules known as secondary metabolites. The present study aims to virtually screen these plant secondary metabolites (PSM) for their possible anti-SARS-CoV-2 properties targeting four proteins/ enzymes which govern viral pathogenesis. Results of molecular docking with 4,704 ligands against four target proteins, and data analysis revealed a unique pattern of structurally similar PSM interacting with the target proteins. Among the top-ranked PSM which recorded lower binding energy (BE), > 50% were triterpenoids which interacted strongly with viral spike protein-receptor binding domain, > 32% molecules which showed better interaction with the active site of human transmembrane serine protease were belongs to flavonoids and their glycosides, > 16% of flavonol glycosides and > 16% anthocyanidins recorded lower BE against active site of viral main protease and > 13% flavonol glycoside strongly interacted with active site of viral RNA-dependent RNA polymerase. The primary concern about these PSM is their bioavailability. However, several PSM recorded higher bioavailability score and found fulfilling most of the drug-likeness characters as per Lipinski's rule (Coagulin K, Kamalachalcone C, Ginkgetin, Isoginkgetin, 3,3'-Biplumbagin, Chrysophanein, Aromoline, etc.). Natural occurrence, bio-transformation, bioavailability of selected PSM and their interaction with the target site of selected proteins were discussed in detail. Present study provides a platform for researchers to explore the possible use of selected PSM to prevent/ cure the COVID-19 by subjecting them for thorough in vitro and in vivo evaluation for the capabilities to interfering with the process of viral host cell recognition, entry and replication.