Mycobacterial FtsEX-RipC interaction is required for normal growth and cell morphology in rifampicin and low ionic strength conditions
ABSTRACTTuberculosis, a lung disease caused by Mycobacterium tuberculosis (Mtb), remains a major global health problem ranking as the second leading cause of death from a single infectious agent. One of the major factors contributing toward Mtb’s success as a pathogen is its unique cell wall and its...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2024-03-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.02515-23 |
| _version_ | 1797276761549963264 |
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| author | Veneshley Samuels Andani E. Mulelu Hlumani Ndlovu Mohlopheni J. Marakalala |
| author_facet | Veneshley Samuels Andani E. Mulelu Hlumani Ndlovu Mohlopheni J. Marakalala |
| author_sort | Veneshley Samuels |
| collection | DOAJ |
| description | ABSTRACTTuberculosis, a lung disease caused by Mycobacterium tuberculosis (Mtb), remains a major global health problem ranking as the second leading cause of death from a single infectious agent. One of the major factors contributing toward Mtb’s success as a pathogen is its unique cell wall and its ability to counteract various arms of the host’s immune response. A recent genome-scale study profiled a list of candidate genes that are predicted to be essential for Mtb survival of host-mediated responses. One candidate was FtsEX, a protein complex composed of an ATP-binding domain, FtsE, and a transmembrane domain, FtsX. FtsEX functions through interaction with a periplasmic hydrolase, RipC. Homologs of FtsEX exist in other bacteria and have been linked with playing a key role in regulating peptidoglycan hydrolysis during cell elongation and division. Here, we report on Mycobacterium smegmatis, FtsE, FtsX, and RipC and their protective roles in stressful conditions. We demonstrate that the individual genes of FtsEX complex and RipC are not essential for survival in normal growth conditions but conditionally essential in low-salt media and antibiotic-treated media. Growth defects in these conditions were characterized by short and bulgy cells as well as elongated filamentous cells. Our results suggest that FtsE, FtsX, and RipC are required for both normal cell elongation and division and ultimately for survival in stressful conditions.IMPORTANCEMycobacterial cell growth and division are coordinated with regulated peptidoglycan hydrolysis. Understanding cell wall gene complexes that govern normal cell division and elongation will aid in the development of tools to disarm the ability of mycobacteria to survive immune-like and antibiotic stresses. We combined genetic analyses and scanning electron microscopy to analyze morphological changes of mycobacterial FtsEX and RipC mutants in stressful conditions. We demonstrate that FtsE, FtsX, FtsEX, and RipC are conditionally required for the survival of Mycobacterium smegmatis during rifampicin treatment and in low-salt conditions. Growth defects in these conditions were characterized by short and bulgy cells as well as elongated filamentous cells. We also show that the FtsEX-RipC interaction is essential for the survival of M. smegmatis in rifampicin. Our results suggest that FtsE, FtsX, and RipC are required for normal cell wall regulation and ultimately for survival in stressful conditions. |
| first_indexed | 2024-03-07T15:33:57Z |
| format | Article |
| id | doaj.art-a8d4d1344b3b4e9ab991fdf2dda071cc |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-07T15:33:57Z |
| publishDate | 2024-03-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-a8d4d1344b3b4e9ab991fdf2dda071cc2024-03-05T14:04:36ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972024-03-0112310.1128/spectrum.02515-23Mycobacterial FtsEX-RipC interaction is required for normal growth and cell morphology in rifampicin and low ionic strength conditionsVeneshley Samuels0Andani E. Mulelu1Hlumani Ndlovu2Mohlopheni J. Marakalala3Division of Medical Microbiology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaDivision of Medical Biochemistry and Structural Biology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaDivision of Chemical Systems Biology, Department of Integrative Biomedical Sciences and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaDivision of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaABSTRACTTuberculosis, a lung disease caused by Mycobacterium tuberculosis (Mtb), remains a major global health problem ranking as the second leading cause of death from a single infectious agent. One of the major factors contributing toward Mtb’s success as a pathogen is its unique cell wall and its ability to counteract various arms of the host’s immune response. A recent genome-scale study profiled a list of candidate genes that are predicted to be essential for Mtb survival of host-mediated responses. One candidate was FtsEX, a protein complex composed of an ATP-binding domain, FtsE, and a transmembrane domain, FtsX. FtsEX functions through interaction with a periplasmic hydrolase, RipC. Homologs of FtsEX exist in other bacteria and have been linked with playing a key role in regulating peptidoglycan hydrolysis during cell elongation and division. Here, we report on Mycobacterium smegmatis, FtsE, FtsX, and RipC and their protective roles in stressful conditions. We demonstrate that the individual genes of FtsEX complex and RipC are not essential for survival in normal growth conditions but conditionally essential in low-salt media and antibiotic-treated media. Growth defects in these conditions were characterized by short and bulgy cells as well as elongated filamentous cells. Our results suggest that FtsE, FtsX, and RipC are required for both normal cell elongation and division and ultimately for survival in stressful conditions.IMPORTANCEMycobacterial cell growth and division are coordinated with regulated peptidoglycan hydrolysis. Understanding cell wall gene complexes that govern normal cell division and elongation will aid in the development of tools to disarm the ability of mycobacteria to survive immune-like and antibiotic stresses. We combined genetic analyses and scanning electron microscopy to analyze morphological changes of mycobacterial FtsEX and RipC mutants in stressful conditions. We demonstrate that FtsE, FtsX, FtsEX, and RipC are conditionally required for the survival of Mycobacterium smegmatis during rifampicin treatment and in low-salt conditions. Growth defects in these conditions were characterized by short and bulgy cells as well as elongated filamentous cells. We also show that the FtsEX-RipC interaction is essential for the survival of M. smegmatis in rifampicin. Our results suggest that FtsE, FtsX, and RipC are required for normal cell wall regulation and ultimately for survival in stressful conditions.https://journals.asm.org/doi/10.1128/spectrum.02515-23FtsEFtsXFtsEXRipCMycobacterium tuberculosisMycobacterium smegmatis |
| spellingShingle | Veneshley Samuels Andani E. Mulelu Hlumani Ndlovu Mohlopheni J. Marakalala Mycobacterial FtsEX-RipC interaction is required for normal growth and cell morphology in rifampicin and low ionic strength conditions Microbiology Spectrum FtsE FtsX FtsEX RipC Mycobacterium tuberculosis Mycobacterium smegmatis |
| title | Mycobacterial FtsEX-RipC interaction is required for normal growth and cell morphology in rifampicin and low ionic strength conditions |
| title_full | Mycobacterial FtsEX-RipC interaction is required for normal growth and cell morphology in rifampicin and low ionic strength conditions |
| title_fullStr | Mycobacterial FtsEX-RipC interaction is required for normal growth and cell morphology in rifampicin and low ionic strength conditions |
| title_full_unstemmed | Mycobacterial FtsEX-RipC interaction is required for normal growth and cell morphology in rifampicin and low ionic strength conditions |
| title_short | Mycobacterial FtsEX-RipC interaction is required for normal growth and cell morphology in rifampicin and low ionic strength conditions |
| title_sort | mycobacterial ftsex ripc interaction is required for normal growth and cell morphology in rifampicin and low ionic strength conditions |
| topic | FtsE FtsX FtsEX RipC Mycobacterium tuberculosis Mycobacterium smegmatis |
| url | https://journals.asm.org/doi/10.1128/spectrum.02515-23 |
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