PMID- 36809827 OWN - NLM STAT- MEDLINE DCOM- 20230724 LR - 20230724 IS - 1638-6183 (Electronic) IS - 0300-9084 (Linking) VI - 211 DP - 2023 Aug TI - Mycobacterium smegmatis secreting methionine sulfoxide reductase A (MsrA) modulates cellular processes in mouse macrophages. PG - 1-15 LID - S0300-9084(23)00048-2 [pii] LID - 10.1016/j.biochi.2023.02.010 [doi] AB - Methionine sulfoxide reductase A (MsrA) is an antioxidant repair enzyme that reduces the oxidized methionine (Met-O) in proteins to methionine (Met). Its pivotal role in the cellular processes has been well established by overexpressing, silencing, and knocking down MsrA or deleting the gene encoding MsrA in several species. We are specifically interested in understanding the role of secreted MsrA in bacterial pathogens. To elucidate this, we infected mouse bone marrow-derived macrophages (BMDMs) with recombinant Mycobacterium smegmatis strain (MSM), secreting a bacterial MsrA or M. smegmatis strain (MSC) carrying only the control vector. BMDMs infected with MSM induced higher levels of ROS and TNF-alpha than BMDMs infected with MSC. The increased ROS and TNF-alpha levels in MSM-infected BMDMs correlated with elevated necrotic cell death in this group. Further, RNA-seq transcriptome analysis of BMDMs infected with MSC and MSM revealed differential expression of protein and RNA coding genes, suggesting that bacterial-delivered MsrA could modulate the host cellular processes. Finally, KEGG pathway enrichment analysis identified the down-regulation of cancer-related signaling genes in MSM-infected cells, indicating that MsrA can potentially regulate the development and progression of cancer. CI - Copyright (c) 2023 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved. FAU - Veerapandian, Raja AU - Veerapandian R AD - Center of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, TX, 79905, USA. FAU - Ramos, Enrique I AU - Ramos EI AD - Center of Emphasis in Cancer, Paul L. Foster School of Medicine, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, TX, 79905, USA. FAU - Vijayaraghavan, Mahalakshmi AU - Vijayaraghavan M AD - Center of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, TX, 79905, USA. FAU - Sedano, Melina J AU - Sedano MJ AD - Center of Emphasis in Cancer, Paul L. Foster School of Medicine, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, TX, 79905, USA. FAU - Carmona, Areanna AU - Carmona A AD - Center of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, TX, 79905, USA. FAU - Chacon, Jessica A AU - Chacon JA AD - Department of Medical Education, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, TX, 79905, USA. FAU - Gadad, Shrikanth S AU - Gadad SS AD - Center of Emphasis in Cancer, Paul L. Foster School of Medicine, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, TX, 79905, USA; Frederick L. Francis Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, Texas, 79905, USA; Mays Cancer Center, UT Health San Antonio MD Anderson Cancer Center, San Antonio, TX, 78229, USA. Electronic address: shrikanth.gadad@ttuhsc.edu. FAU - Dhandayuthapani, Subramanian AU - Dhandayuthapani S AD - Center of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, TX, 79905, USA; Frederick L. Francis Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, Texas, 79905, USA. Electronic address: s.dhandayuthapani@ttuhsc.edu. LA - eng PT - Journal Article DEP - 20230219 PL - France TA - Biochimie JT - Biochimie JID - 1264604 RN - AE28F7PNPL (Methionine) RN - EC 1.8.4.- (Methionine Sulfoxide Reductases) RN - 0 (Reactive Oxygen Species) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Mice MH - *Macrophages/microbiology MH - Methionine/metabolism MH - *Methionine Sulfoxide Reductases/genetics/metabolism MH - *Mycobacterium smegmatis/enzymology/genetics MH - Oxidative Stress MH - Reactive Oxygen Species/metabolism MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - MsrA OT - Mycobacterium smegmatis OT - Necrosis OT - RNA-Seq OT - ROS OT - Secretion OT - Transcriptome COIS- Declaration of competing interest "The authors declare no conflict of interest." EDAT- 2023/02/23 06:00 MHDA- 2023/07/10 06:42 CRDT- 2023/02/22 14:11 PHST- 2022/11/15 00:00 [received] PHST- 2023/02/16 00:00 [revised] PHST- 2023/02/17 00:00 [accepted] PHST- 2023/07/10 06:42 [medline] PHST- 2023/02/23 06:00 [pubmed] PHST- 2023/02/22 14:11 [entrez] AID - S0300-9084(23)00048-2 [pii] AID - 10.1016/j.biochi.2023.02.010 [doi] PST - ppublish SO - Biochimie. 2023 Aug;211:1-15. doi: 10.1016/j.biochi.2023.02.010. Epub 2023 Feb 19.