Project description:The increasing rate of antibiotic-resistant bacteria has become a serious health threat. Thus, it is important to discover, characterize, and optimize new molecules to overcome infections caused by these bacteria. It is known that Acinetobacter baumannii has a high capacity to avoid antibacterial drugs. Consequently, these bacteria have emerged as one of responsible for hospital and community-acquired infections. However, how this pathogen infects and survives inside the host cell is unknown. Here we analyze the time-resolved transcriptional profile changes on human epithelial HeLa cells after A. baumannii. Our results show how A.baumannii can survive in host cells and starts replication at 4 hours post infection. We sequenced RNA to obtain a set of differentially expressed gen (DEGs) used for a Gene Ontology (GO) and KEGG pathway analysis. The results show us how host bacteria is altering the host cells environment for their own benefit. We also determine chromosomal regions affected by our set of genes. Furthermore, we obtain protein-protein networks that reveal highly interacted proteins. The combination of these results will pave the way to discover new antimicrobial candidates for multidrug-resistant bacteria.
Project description:The widespread presence of antibiotic-resistant bacteria in the environment has been recognized as an important emerging environmental contaminant. Hospital wards, as a special public indoor environment, are of great concern for the risks associated with this emerging environmental contaminant. Pseudomonas aeruginosa, a common nosocomial bacterium, is a contamination risk in the hospital environment due to its drug resistance and transmission of virulence factors. Notably, the antimicrobial peptide-sensing two-component system (TCS) ParRS and CprRS have been implicated in dynorphin-induced signaling, but the underlying Manuscript2 mechanism has remained elusive. In this study, we performed proteomic analysis to systematically investigate the contributions of ParRS and CprRS to P. aeruginosa pathogenesis and dynorphin-induced resistance to polymyxins. Additionally, we characterized the significance of the extracellular sensor domains of ParS and CprS in dynorphin perception. Furthermore, through structural biology, we identified additional TCS sensors with similar extracellular domain conformations, which also directly interacted with dynorphin in vitro. This suggests convergent evolution in different bacterial TCSs for host-derived synthetic peptide signal transmitting. Our findings establish a link between CAMPs resistance associated TCSs and virulence regulation of common nosocomial bacteria. This further illustrates the danger of this emerging contaminant for the environment and humans.
Project description:This study aims to determine the epidemiology of Enterobacteriaceae resistant to antibiotics of last resort in pregnant women in labour at a tertiary hospital, Pretoria, South Africa. Rectal swabs shall be used to screen for colonisation with CRE and colistin-resistant Enterobacteriales in pregnant women during labour. Carbapenem and colistin-resistant Enterobacterales can cause the following infections: bacteraemia; nosocomial pneumonia; urinary tract infections, and intra-abdominal infections. Due to limited treatment options, infections caused by these multidrug-resistant organisms are associated with a mortality rate of 40-50%. Screening for colonisation of carbapenem-resistant Enterobacteriaceae (CRE) and colistin-resistant Enterobacteriaceae will help implement infection and prevention measures to limit the spread of these multidrug-resistant organisms.
Project description:Incomplete antibiotic removal in pharmaceutical wastewater treatment plants (PWWTPs) could lead to the development and spread of antibiotic-resistant bacteria (ARBs) and genes (ARGs) in the environment, posing a growing public health threat. In this study, two multiantibiotic-resistant bacteria, Ochrobactrum intermedium (N1) and Stenotrophomonas acidaminiphila (N2), were isolated from the sludge of a PWWTP in Guangzhou, China. The N1 strain was highly resistant to ampicillin, cefazolin, chloramphenicol, tetracycline, and norfloxacin, while the N2 strain exhibited high resistance to ampicillin, chloramphenicol, and cefazolin. Whole-genome sequencing revealed that N1 and N2 had genome sizes of 0.52 Mb and 0.37 Mb, respectively, and harbored 33 and 24 ARGs, respectively. The main resistance mechanism in the identified ARGs included efflux pumps, enzymatic degradation, and target bypass, with the N1 strain possessing more multidrug-resistant efflux pumps than the N2 strain (22 vs 12). This also accounts for the broader resistance spectrum of N1 than of N2 in antimicrobial susceptibility tests. Additionally, both genomes contain numerous mobile genetic elements (89 and 21 genes, respectively) and virulence factors (276 and 250 factors, respectively), suggesting their potential for horizontal transfer and pathogenicity. Overall, this research provides insights into the potential risks posed by ARBs in pharmaceutical wastewater and emphasizes the need for further studies on their impact and mitigation strategies.