Multiomics characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolates with heterogeneous intermediate resistance to vancomycin (hVISA) in Latin America.

BACKGROUND: Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) compromise the clinical efficacy of vancomycin. The hVISA isolates spontaneously produce vancomycin-intermediate Staphylococcus aureus (VISA) cells generated by diverse and intriguing mechanisms. OBJECTIVE: To characterize the biomolecular profile of clinical hVISA applying genomic, transcriptomic and metabolomic approaches. METHODS: 39 hVISA and 305 VSSA and their genomes were included. Core genome-based Bayesian phylogenetic reconstructions were built and alterations in predicted proteins in VISA/hVISA were interrogated. Linear discriminant analysis and a Genome-Wide Association Study were performed. Differentially expressed genes were identified in hVISA-VSSA by RNA-sequencing. The undirected profiles of metabolites were determined by liquid chromatography and hydrophilic interaction in six CC5-MRSA. RESULTS: Genomic relatedness of MRSA associated to hVISA phenotype was not detected. The change Try38 → His in Atl (autolysin) was identified in 92% of the hVISA. We identified SNPs and k-mers associated to hVISA in 11 coding regions with predicted functions in virulence, transport systems, carbohydrate metabolism and tRNA synthesis. Further, capABCDE, sdrD, esaA, esaD, essA and ssaA genes were overexpressed in hVISA, while lacABCDEFG genes were downregulated. Additionally, valine, threonine, leucine tyrosine, FAD and NADH were more abundant in VSSA, while arginine, glycine and betaine were more abundant in hVISA. Finally, we observed altered metabolic pathways in hVISA, including purine and pyrimidine pathway, CoA biosynthesis, amino acid metabolism and aminoacyl tRNA biosynthesis. CONCLUSIONS: Our results show that the mechanism of hVISA involves major changes in regulatory systems, expression of virulence factors and reduction in glycolysis via TCA cycle. This work contributes to the understanding of the development of this complex resistance mechanism in regional strains.

[Epidemiologic and situational panorama of hepatitis C in Mexico]. / Panorama epidemiológico y situacional de la hepatitis C en México.

OBJECTIVE: To determine the epidemiological situation of Chronic Hepatitis C (CHC) in our country. BACKGROUND DATA: Chronic Hepatitis C affects 170 million people worldwide, and about 0.7% of Mexican population. There is no enough epidemiological information about CHC in our country, and it is very probable that some cases are not even detected. METHODS: An investigation poll was performed. Age, gender, birthday, weight, race, residence and birth place, routes of transmission, ALT levels, histological, serological and molecular diagnosis, evidence of complications and previous treatments were recorded. A data recollection sheet was dispatched to different country provinces; they had 6 months to answer it, in order to recollect all information. RESULTS: 831 patients were analized (58.6% female and 41.4% male) with the following distribution in our country provinces: Aguascalientes 15, Chihuahua 12, Distrito Federal 495, Durango 10, Jalisco 89, Guanajuato 78, Yucatán 8, Querétaro 11, Sonora 40, Tabasco 15, Baja California 5, Veracruz 13, Tamaulipas 2 and 38 patients of Nuevo León. The highest incidence of CHC was found at fifth and sixth decade of life (28.5% y 26.7% respectively. The weight distribution was 36.2% < 65kg, 34.6% 65-75 kg and 29.2% > 75 kg. 86.5% had chronic hepatitis and 13.2% cirrhosis. The risk factors for HCV infection analysis showed that the main route of transmission was via contaminated blood (64.2%); when we excluded the patients that were exposed before 1995, the incidence was lowered to 4.5%. The higher incidence was showed between 1970 and 1990 (68%). The intravenous drug users were predominantly male and on those patients in the provinces near the north border line of our country. The predominant genotype was gen- 1 no matter the province (72.2%), in the intravenous drug users genotype 3 was found in 25%. The viral load was similar in all the provinces. 75% of the patients had have treatment and 22.5% had have two cycles, 50% of cirrhotic patients had have treatment whereas only 28% of the patients with late complications had have it. The most common treatment was pegylated alpha-2a interferon plus ribavirine. CONCLUSIONS: 1. The main route of transmission was blood transfusion. There is a marked decrease in the incidence of post-transfusional hepatitis since the introduction of anti-VHC antibody screening of blood donors (4.5%). 2. The time between the infection and diagnosis was 23 years for chronic hepatitis and 26 years for cirrhosis. 3. Intravenous drugs use was an important route of transmission in the north of our country. 4. The predominant genotype was gen-1. 5. Almost all the patients with chronic hepatitis received treatment, the most common used was pegylated interferon alpha-2a and ribavirin. 6.50% of the patients with CHC have late complications.