Reactive oxygen species

Oxidative damage can have a devastating effect on the structure and activity of proteins, and may even lead to cell death. The sulfur-containing amino acids cysteine and methionine are particularly susceptible to reactive oxygen species (ROS) and reactive chlorine species (RCS), which can damage proteins. In this Review, we discuss our current understanding of the reducing systems that enable bacteria to repair oxidatively damaged cysteine and methionine residues in the cytoplasm and in the bacterial cell envelope. We highlight the importance of these repair systems in bacterial physiology and virulence, and we discuss several examples of proteins that become activated by oxidation and help bacteria to respond to oxidative stress.

Oxidative stress, protein damage and repair in bacteria

In the twenty-first century, the clinical microbiology laboratory plays a central part in optimizing the management of infectious diseases and surveying local and global epidemiology. This pivotal role is made possible by the adoption of rational sampling, point-of-care tests, extended automation and new technologies, including mass spectrometry for colony identification, real-time genomics for isolate characterization, and versatile and permissive culture systems. When balanced with cost, these developments can improve the workflow and output of clinical microbiology laboratories and, by identifying and characterizing microbial pathogens, provide significant input to scientific discovery.

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Modern clinical microbiology: new challenges and solutions

It is important to realize that leishmaniasis guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The IDSA and ASTMH consider adherence to these guidelines to be voluntary, with the ultimate determinations regarding their application to be made by the physician in the light of each patient's individual circumstances.

Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH)

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Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH)*

Evaluation of rK28 antigen for serodiagnosis of visceral Leishmaniasis in India

Transcriptional dysregulation in Huntington's disease: a failure of adaptive transcriptional homeostasis.

Staphylococcus aureus is a major human pathogen and emergence of antibiotic resistance in clinical staphylococcal isolates raises concerns about our ability to control these infections. Cell wall-active antibiotics cause elevated synthesis of methionine sulfoxide reductases (Msrs: MsrA1 and MsrB) in S. aureus. MsrA and MsrB enzymes reduce S-epimers and R-epimers of methionine sulfoxide, respectively, that are generated under oxidative stress. In the S. aureus chromosome, there are three msrA genes (msrA1, msrA2 and msrA3) and one msrB gene. To understand the precise physiological roles of Msr proteins in S. aureus, mutations in msrA1, msrA2 and msrA3 and msrB genes were created by site-directed mutagenesis. These mutants were combined to create a triple msrA (msrA1, msrA2 and msrA3) and a quadruple msrAB (msrA1, msrA2, msrA3, msrB) mutant. These mutants were used to determine the roles of Msr proteins in staphylococcal growth, antibiotic resistance, adherence to human lung epithelial cells, pigment production, and survival in mice relative to the wild-type strains. MsrA1-deficient strains were sensitive to oxidative stress conditions, less pigmented and less adherent to human lung epithelial cells, and showed reduced survival in mouse tissues. In contrast, MsrB-deficient strains were resistant to oxidants and were highly pigmented. Lack of MsrA2 and MsrA3 caused no apparent growth defect in S. aureus. In complementation experiments with the triple and quadruple mutants, it was MsrA1 and not MsrB that was determined to be critical for adherence and phagocytic resistance of S. aureus. Overall, the data suggests that MsrA1 may be an important virulence factor and MsrB probably plays a balancing act to counter the effect of MsrA1 in S. aureus.

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Significance of four methionine sulfoxide reductases in Staphylococcus aureus.

Previously developed methods for noninvasive PCR diagnosis of visceral leishmaniasis (VL) have significant limitations. Diagnosis of VL using PCR and buccal swabs was evaluated in 307 subjects, including 148 patients confirmed to have VL. This method is simple and well tolerated and has good potential for development, showing 83% sensitivity with 90.56% specificity in control groups.

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Noninvasive molecular diagnosis of human visceral leishmaniasis

Nitric oxide and its derivative peroxynitrites are generated by host defense system to control bacterial infection. However certain Gram positive bacteria including Staphylococcus aureus possess a gene encoding nitric oxide synthase (SaNOS) in their chromosome. In this study it was determined that under normal growth conditions, expression of SaNOS was highest during early exponential phase of the bacterial growth. In oxidative stress studies, deletion of SaNOS led to increased susceptibility of the mutant cells compared to wild-type S. aureus. While inhibition of SaNOS activity by the addition of L-NAME increased sensitivity of the wild-type S. aureus to oxidative stress, the addition of a nitric oxide donor, sodium nitroprusside, restored oxidative stress tolerance of the SaNOS mutant. The SaNOS mutant also showed reduced survival after phagocytosis by PMN cells with respect to wild-type S. aureus.

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Manisha Vaish

Papers

Evaluation of rK28 antigen for serodiagnosis of visceral Leishmaniasis in India

Transcriptional dysregulation in Huntington's disease: a failure of adaptive transcriptional homeostasis.

Significance of four methionine sulfoxide reductases in Staphylococcus aureus.

Noninvasive molecular diagnosis of human visceral leishmaniasis

Antioxidant Functions of Nitric Oxide Synthase in a Methicillin Sensitive Staphylococcus aureus.