RESUMEN
Burkholderia mallei is an aerobic, Gram-negative, non-motile bacillus. As an obligate mammalian pathogen, it primarily affects solipeds. Although rarely transmitted to humans, the disease it causes, glanders, is classified as a zoonosis. The bacterium was officially eradicated in Brazil in 1969; however, it reemerged after three decades. This study aims to assess the virulence of a specific B. mallei strain, isolated in Brazil, in BALB/c mice through intranasal infection. The strain, B. mallei BAC 86/19, was obtained from the tracheal secretion of a young mare displaying positive serology but no clinical signs of glanders. Post-mortem examinations revealed macroscopic lesions consistent with the disease, however. In mice, the LD50 was determined to be approximately 1.59 × 105 colony-forming units (CFU)/animal. Mice exposed to either 0.1 × LD50 or 1 × LD50 displayed transient weight loss, which resolved after three or five days, respectively. B. mallei persisted within the liver and lung for five days post-infection and in the spleen for seven days. These findings underscore the detectable virulence of the Brazilian B. mallei BAC 86/19 strain in mice, which are relatively resilient hosts. This research points to the importance of the continued investigation of the virulence mechanisms and potential countermeasures associated with B. mallei infections, including their Brazilian isolates.
RESUMEN
NDM-1 comprises a carbapenemase that was first detected in 2008 in New Delhi, India. Since then, NDM-1-producing Klebsiella pneumoniae strains have been reported in many countries and usually associated with intra and inter-hospital dissemination, along with travel-related epidemiological links. In South America, Brazil represents the largest reservoir of NMD-1-producing K. pneumoniae. Here, we focused on the detection and molecular/structural characterization of the blaNDM-1 resistance gene/enzyme from 24 K. pneumoniae clinical isolates in the Midwest region of Brazil. Antimicrobial susceptibility assays showed that all isolates are resistant to carbapenems. Molecular typing of the isolates revealed seven clonal groups among the K. pneumoniae isolates, which may indicate intra or inter-hospital dissemination. Moreover, the blaNDM-1 gene was detected in all 24 K. pneumoniae isolates and the full blaNDM-1 gene was cloned. Bioinformatics analysis showed that the NDM-1 enzyme sequence found in our isolates is highly conserved when compared to other NDM-1 enzymes. In addition, molecular docking studies indicate that the NDM-1 identified binds to different carbapenems through hydrogen and zinc coordination bonds. In summary, we present the molecular characterization of NDM-1-producing K. pneumoniae strains isolated from different hospitals, also providing atomic level insights into molecular complexes NDM-1/carbapenem antibiotics.