| Congresso Brasileiro de Microbiologia 2023 | Resumo: 1148-1 | ||||
Resumo:Globally, urinary tract infections (UTI) affect approximately 150 million people every year. Uropathogenic Escherichia coli (UPEC) is responsible for more than 80% of these infections, which causes an augment in hospitalizations and medical expenses. UPEC infections are a major public health concern in infectious diseases and one of the most prevalent bacterial pathogens during human infections. It is also linked to a recent significant increase in bacterial resistance to several major classes of antimicrobials. Likely, the use of last resources antibiotics during bacterial infections has augmented drastically due to frequent isolation of multidrug resistant bacteria. Herein, our goal was unravelling novel mechanisms of virulence in KPC-2 UPEC ST131 in vitro and in vivo, specifically in the alternative model of wax moth, the Galleria melonella species. We have assessed heteroresistance (HR) phenotype via population analysis profiling (PAP) of UPEC clinical isolates, the A20 and A30 were selected for further studies from the FAMERP Hospital. We used here Gram-negative bacteria last resource antibiotics such as cationic antimicrobial peptides (CAMP), e.g. polymyxin B and colistin. They are frequently linked with LPS modifications, and here we observed the role of the Lipid-A phosphoethanolamine transferase, the EptA protein and the polymyxin resistance two-component system PmrAB directly linked HR phenotype. Transcriptomic analyses confirmed their role showing a drastic 5- fold and 2-fold increase respectively in eptA and pmrB<,/i> expression levels for the A20 and A30 clinical strains in the presence of Colistin (8.0mcg/ml and 32mcg/ml respectively). Type 1 fimbriae (T1F) functionality studies were also conducted here, since T1F are essential to initiate urinary tract colonization and cell invasion to form intracellular bacterial communities (IBCs) in UPEC. We have employed the α-methyl D-mannoside to block T1F has presented a drastic reduction in the invasion assays and IBC formation.
In summary, the study brings novel insights in the pathogenesis and heteroresistant to CAMP of clinically relevant strains isolated in Brazil. Altogether, our data will help to further elucidate these novel mechanisms and contribute with infectious diseases fight against bacterial resistance. Most importantly a more comprehensive analysis of new targets for the rational development of novel antimicrobials and alternative therapies.
Palavras-chave: pathogenicity, virulence, bacterial resistance, heteroresistance, MDR bacteria Agência de fomento:Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) | |||||