A comprehensive review of genomics, transcriptomics, proteomics, and metabolomic insights into the differentiation of Pseudomonas aeruginosa from the planktonic to biofilm state: A multi-omics approach.

Biofilm formation by Pseudomonas aeruginosa is primarily responsible for chronic wound and lung infections in humans. These infections are persistent owing to the biofilm's high tolerance to antimicrobials and constantly changing environmental factors. Understanding the mechanism governing biofilm formation can help to develop therapeutics explicitly directed against the molecular markers responsible for this process. After numerous years of research, many genes responsible for both in vitro and in vivo biofilm development remain unidentified. However, there is no "all in one" complete in vivo or in vitro biofilm model. Recent findings imply that the shift from planktonic bacteria to biofilms is a complicated and interrelated differentiation process. Research on the applications of omics technologies in P. aeruginosa biofilm development is ongoing, and these approaches hold great promise for expanding our knowledge of the mechanisms of biofilm formation. This review discusses the different factors that affect biofilm formation and compares P. aeruginosa biofilm formation using the omics approaches targeting essential biological macromolecules, such as DNA, RNA, Protein, and metabolome. Furthermore, we have outlined the application of currently available omics tools, such as genomics, proteomics, metabolomics, transcriptomics, and integrated multi-omics methodologies, to understand the differential gene expression (biofilm vs. planktonic bacteria) of P. aeruginosa biofilms.

Integration of phenotypic, qPCR and genome sequencing methodologies for the detection of antimicrobial resistance and virulence in clinical isolates of a tertiary hospital, India.

The emergence of antimicrobial resistance (AMR) and virulence in clinical isolates is a significant public health concern. The rapid and accurate detection of these traits in clinical isolates is essential for effective infection control and treatment. We demonstrated the integration of multiple detection methodologies, including phenotypic testing, quantitative polymerase chain reaction (qPCR), and genome sequencing, to detect AMR and virulence in clinical isolates. One hundred sixty-two gram-negative bacterial clinical isolates were selected for this study from the Shri Vinoba Bhave Civil Hospital, Silvassa, a tertiary government hospital. Antimicrobial susceptibility was detected by determining the Minimum Inhibitory Concentration (MIC) using Vitek-2, whereas the combined disk (CD) method was used for phenotypic detection of carbapenemase activity. The highest sensitivity rates were obtained for antibiotics colistin 87.93%, amikacin 67.52%, tigecycline 63.39%, nitrofurantoin 60.87%, and gentamycin 56.08%. The most resistant antibiotics were ceftazidime (71.93%), ciprofloxacin (67.95%) and trimethoprim/sulfamethoxazole (65.56%). Approximately 46.91% (76) of all the isolates were MBL isolates. The qPCR results confirmed the presence of blaNDM-1 in 29.01% of the isolates. The blaNDM-1 harbouring isolates in descending order, were Acinetobacter, Enterobacter cloacae, and Klebsiella pneumoniae. Klebsiella and Acinetobacter isolates were extensively drug-resistant. Whole genome sequencing performed on one of the Klebsiella pneumoniae isolates revealed the presence of many virulence factors, which increased the pathogenicity of the clinical isolates. The results showed that antimicrobial resistance, including carbapenem resistance, blaNDM-1, and virulence factors, was highly prevalent among isolates from tertiary clinical hospitals. The integration of multiple detection methodologies can potentially improve the detection of AMR and virulence in clinical isolates, leading to better patient outcomes and a reduced spread of these essential traits.

Preclinical safety, pharmacokinetics and antitumor efficacy profile of liposome-entrapped SN-38 formulation.

BACKGROUND: SN-38, 7-ethyl-10-hydroxycamptothecin, is a biologically active metabolite of irinotecan. Its poor solubility restricted its development as an anticancer agent. We have developed an easy-to-use liposome-entrapped SN-38 (LE-SN38) and evaluated its toxicology, pharmacokinetics and antitumor efficacy profile. MATERIALS AND METHODS: Toxicity and pharmacokinetics studies were conducted in CD2F1 mice and beagle dogs. Therapeutic efficacy studies were performed in murine leukemia (P388 and P388/ADR) and in a human pancreatic (Capan-1) tumor models. RESULTS: Multiple dose administration (i.v. x 5) of LE-SN38 indicated a maximum tolerated dose (MTD) of 5.0 and 7.5 mg/kg/day for male and female mice, respectively. The MTD of LE-SN38 in dogs was 1.2 mg/kg. The elimination half-life (t1/2) of SN-38 in mouse plasma was 6.38 h with volume of distribution (VdSS) 2.55 L/kg. In dogs, t1/2 and VdSS were 1.38-6.42 h and 1.69-5.01 L/kg; respectively. P388 tumor-bearing mice dosed with LE-SN38 at 5.5 mg/kg (i.v. x 5) showed 100% survival. LE-SN38 at 4 or 8 mg/kg (i. v. x 5) inhibited 65% and 98% tumor growth, respectively, in a human pancreatic tumor model. CONCLUSION: LE-SN38 showed a favorable pharmacokinetics profile and can be administered safely at therapeutically effective doses.