Pyrazinamide (PZA) is one of the most important drugs used in combined antituberculous therapy. After the drug enters Mycobacterium tuberculosis it is hydrolyzed by pyrazinamidase (PZAse) to the bactericidal molecule pyrazinoic acid (POA).Ribosomal protein S1 (RpsA) was recently identified as a possible target of PZA based on its binding activity to POA and capacity to inhibit trans-translation. However, its role is not completely understood. It has been proposed thatMycobacterium smegmatis RpsA is not capable of binding POA, unlike M. tuberculosis RpsA. This may be due to the different amino acid sequence in the carboxy-terminal region of the two molecules: in M. smegmatis RpsA it is much closer to the sites that may interact with POA than in M. tuberculosis RpsA. These differences could be contributing, along with the presence of highly active POA efflux, to the natural resistance to PZA in M. smegmatis. To further understand the mechanisms of action of PZA and the role of RpsA in PZA susceptibility, we evaluated the effect of complementing M. tuberculosis RpsA expression in M. smegmatis using pNIT mycobacterial non-integrative expression vector and then performed a PZA susceptibility test determining the minimum inhibitory concentration (MIC) of PZA. It was expected that chimeric ribosomes comprising M.tuberculosis RpsA may be present and may affect PZA susceptibility.Our results showed a reduction in PZA MIC in M. smegmatis complemented with overexpressed M. tuberculosis RpsA compared to non-overexpressed M. smegmatis (468 µg/mL and >7500 µg/mL respectively).
Background. The devastating repercussions of COVID-19 were felt in developing nations like Peru. However, few studies have been conducted in these countries. To make good decisions about public health, it is important to understand how the disease is spread in our area. Methodology/Principal findings. An observational, cross-sectional study was performed between November 11th and November 30th, 2020. In Puerto Pizarro, one out of every four homes was invited to participate in a systematic randomized sampling. Individuals were screened for the qualitative detection of anti-SARS-CoV-2 nucleocapsid (N) protein antibodies and anti-SARS-CoV-2 spike RBD with a rapid chromatographic immunoassay. An adult of legal age was selected, and an additional molecular test (RT-PCR) was taken to look for active COVID-19 cases. Conclusions/Significance. This study shows an adjusted seroprevalence of 24.72% posterior to the first wave of COVID-19 in Tumbes. When adjusted by participant characteristics, women had higher adjusted seroprevalence compared to men (213/356 vs 143/356 [28.01 % vs 21.18 %], p=0.005). More than 20% of IgG seropositive cases belong to the age group under 16 years old. Asymptomatic individuals with recent infections were 66.3% (IgM and IgM/IgG) across all age groups. No association between positive seroprevalence and water supply, water resources, or sanitation services was found. The information is relevant to the Ministry of Health's establishment of a regional program of COVID-19 control and strategic interventions, targeting vulnerable groups and improving vaccination campaigns.
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