Differential Frequencies of HLA-DRB1, DQA1, and DQB1 Alleles and Haplotypes Are Observed in the Arbovirus-Related Neurological Syndromes.

BACKGROUND: We took advantage of the 2015-2016 Brazilian arbovirus outbreak (Zika [ZIKV]/dengue/chikungunya viruses) associated with neurological complications to type HLA-DRB1/DQA1/DQB1 variants in patients exhibiting neurological complications and in bone marrow donors from the same endemic geographical region. METHODS: DRB1/DQA1/DQB1 loci were typed using sequence-specific oligonucleotides. In silico studies were performed using X-ray resolved dimer constructions. RESULTS: The DQA1*01, DQA1*05, DQB1*02, or DQB1*06 genotypes/haplotypes and DQA1/DQB1 haplotypes that encode the putative DQA1/DQB1 dimers were overrepresented in the whole group of patients and in patients exhibiting peripheral neurological spectrum disorders (PSD) or encephalitis spectrum disorders (ESD). The DRB1*04, DRB1*13, and DQA1*03 allele groups protected against arbovirus neurological manifestation, being underrepresented in whole group of patients and ESD and PSD groups. Genetic and in silico studies revealed that DQA1/DQB1 dimers (1) were primarily associated with susceptibility to arbovirus infections; (2) can bind to a broad range of ZIKV peptides (235 of 1878 peptides, primarily prM and NS2A); and (3) exhibited hydrophilic and highly positively charged grooves when compared to the DRA1/DRB1 cleft. The protective dimer (DRA1/DRB1*04) bound a limited number of ZIKV peptides (40 of 1878 peptides, primarily prM). CONCLUSION: Protective haplotypes may recognize arbovirus peptides more specifically than susceptible haplotypes.

In vitro evaluation of mercury (Hg2+) effects on biofilm formation by clinical and environmental isolates of Klebsiella pneumoniae.

The increase in urbanization and industrialization has contributed to the contamination of different environments by means of xenobiotic compounds, such as heavy metals, causing changes in microbial communities. Among these metals, the Mercury (Hg2+) is one the most prevalent toxic metals for the environment The present study aimed to evaluate the effect of mercury on the formation of biofilm by environmental (collected from urban stream water) and clinical isolates of Klebsiella pneumoniae. In addition, antibiotic resistance, virulence factors, and genetic diversity were investigated. Taxonomic identity of eight isolates (one reference, two clinical, and five environmental isolates) was performed by MALDI-TOF-MS, while the antibiotic susceptibility profile was assessed by the disc diffusion method. The ability to form biofilms was evaluated by culture on Congo red agar and by crystal violet staining. Biofilm structure was analyzed by scanning electron microscopy. The hydrophobicity profile and the presence of the virulence genes cps, fimH, and mrkD was investigated. The presence of merA and its relationship with antimicrobial resistance were also assessed. The identity of all isolates was confirmed by MALDI-TOF-MS, and different profiles of resistance to mercury and antibiotics as well as of biofilm formation were identified for the clinical and environmental isolates. All isolates were hydrophilic and positive for the virulence genes cps, fimH, and mrkD; only the clinical isolate K36-A2 was positive for merA. The diversity of the isolates was confirmed by ERIC-PCR, which revealed high heterogeneity among the isolates. In conclusion, the data demonstrate that the investigated isolates present different responses to exposure to Hg2+ and correspond to distinct populations of K. pneumoniae disseminated in the investigated environment. The data obtained in this work will aid in understanding the mechanisms of survival of this pathogen under adverse conditions.