Iron-Induced Respiration Promotes Antibiotic Resistance in Actinomycete Bacteria
ABSTRACT The bacterial response to antibiotics eliciting resistance is one of the key challenges in global health. Despite many attempts to understand intrinsic antibiotic resistance, many of the underlying mechanisms still remain elusive. In this study, we found that iron supplementation promoted a...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-04-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.00425-22 |
| _version_ | 1817991226416168960 |
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| author | Joon-Sun Choi Yeong-Jae Seok You-Hee Cho Jung-Hye Roe |
| author_facet | Joon-Sun Choi Yeong-Jae Seok You-Hee Cho Jung-Hye Roe |
| author_sort | Joon-Sun Choi |
| collection | DOAJ |
| description | ABSTRACT The bacterial response to antibiotics eliciting resistance is one of the key challenges in global health. Despite many attempts to understand intrinsic antibiotic resistance, many of the underlying mechanisms still remain elusive. In this study, we found that iron supplementation promoted antibiotic resistance in Streptomyces coelicolor. Iron-promoted resistance occurred specifically against bactericidal antibiotics, irrespective of the primary target of antibiotics. Transcriptome profiling revealed that some genes in the central metabolism and respiration were upregulated under iron-replete conditions. Iron supported the growth of S. coelicolor even under anaerobic conditions. In the presence of potassium cyanide, which reduces aerobic respiration of cells, iron still promoted respiration and antibiotic resistance. This suggests the involvement of a KCN-insensitive type of respiration in the iron effect. This phenomenon was also observed in another actinobacterium, Mycobacterium smegmatis. Taken together, these findings provide insight into a bacterial resistance strategy that mitigates the activity of bactericidal antibiotics whose efficacy accompanies oxidative damage by switching the respiration mode. IMPORTANCE A widely investigated mode of antibiotic resistance occurs via mutations and/or by horizontal acquisition of resistance genes. In addition to this acquired resistance, most bacteria exhibit intrinsic resistance as an inducible and adaptive response to different classes of antibiotics. Increasing attention has been paid recently to intrinsic resistance mechanisms because this may provide novel therapeutic targets that help rejuvenate the efficacy of the current antibiotic regimen. In this study, we demonstrate that iron promotes the intrinsic resistance of aerobic actinomycetes Streptomyces coelicolor and Mycobacterium smegmatis against bactericidal antibiotics. A surprising role of iron to increase respiration, especially in a mode of using less oxygen, appears a fitting strategy to cope with bactericidal antibiotics known to kill bacteria through oxidative damage. This provides new insights into developing antimicrobial treatments based on the availability of iron and oxygen. |
| first_indexed | 2024-04-14T01:10:34Z |
| format | Article |
| id | doaj.art-acd184919c3243c6b7ecf7715cb36332 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-14T01:10:34Z |
| publishDate | 2022-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-acd184919c3243c6b7ecf7715cb363322022-12-22T02:21:06ZengAmerican Society for MicrobiologymBio2150-75112022-04-0113210.1128/mbio.00425-22Iron-Induced Respiration Promotes Antibiotic Resistance in Actinomycete BacteriaJoon-Sun Choi0Yeong-Jae Seok1You-Hee Cho2Jung-Hye Roe3Laboratory of Molecular Microbiology, School of Biological Sciences, College of Natural Sciences and Institute of Microbiology, Seoul National University, Seoul, South KoreaLaboratory of Microbial Physiology, School of Biological Sciences, College of Natural Sciences and Institute of Microbiology, Seoul National University, Seoul, South KoreaDepartment of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam, Gyeonggi-do, South KoreaLaboratory of Molecular Microbiology, School of Biological Sciences, College of Natural Sciences and Institute of Microbiology, Seoul National University, Seoul, South KoreaABSTRACT The bacterial response to antibiotics eliciting resistance is one of the key challenges in global health. Despite many attempts to understand intrinsic antibiotic resistance, many of the underlying mechanisms still remain elusive. In this study, we found that iron supplementation promoted antibiotic resistance in Streptomyces coelicolor. Iron-promoted resistance occurred specifically against bactericidal antibiotics, irrespective of the primary target of antibiotics. Transcriptome profiling revealed that some genes in the central metabolism and respiration were upregulated under iron-replete conditions. Iron supported the growth of S. coelicolor even under anaerobic conditions. In the presence of potassium cyanide, which reduces aerobic respiration of cells, iron still promoted respiration and antibiotic resistance. This suggests the involvement of a KCN-insensitive type of respiration in the iron effect. This phenomenon was also observed in another actinobacterium, Mycobacterium smegmatis. Taken together, these findings provide insight into a bacterial resistance strategy that mitigates the activity of bactericidal antibiotics whose efficacy accompanies oxidative damage by switching the respiration mode. IMPORTANCE A widely investigated mode of antibiotic resistance occurs via mutations and/or by horizontal acquisition of resistance genes. In addition to this acquired resistance, most bacteria exhibit intrinsic resistance as an inducible and adaptive response to different classes of antibiotics. Increasing attention has been paid recently to intrinsic resistance mechanisms because this may provide novel therapeutic targets that help rejuvenate the efficacy of the current antibiotic regimen. In this study, we demonstrate that iron promotes the intrinsic resistance of aerobic actinomycetes Streptomyces coelicolor and Mycobacterium smegmatis against bactericidal antibiotics. A surprising role of iron to increase respiration, especially in a mode of using less oxygen, appears a fitting strategy to cope with bactericidal antibiotics known to kill bacteria through oxidative damage. This provides new insights into developing antimicrobial treatments based on the availability of iron and oxygen.https://journals.asm.org/doi/10.1128/mbio.00425-22Streptomycesantibiotic resistancebactericidal antibioticiron-induced respirationactinomycetesiron |
| spellingShingle | Joon-Sun Choi Yeong-Jae Seok You-Hee Cho Jung-Hye Roe Iron-Induced Respiration Promotes Antibiotic Resistance in Actinomycete Bacteria mBio Streptomyces antibiotic resistance bactericidal antibiotic iron-induced respiration actinomycetes iron |
| title | Iron-Induced Respiration Promotes Antibiotic Resistance in Actinomycete Bacteria |
| title_full | Iron-Induced Respiration Promotes Antibiotic Resistance in Actinomycete Bacteria |
| title_fullStr | Iron-Induced Respiration Promotes Antibiotic Resistance in Actinomycete Bacteria |
| title_full_unstemmed | Iron-Induced Respiration Promotes Antibiotic Resistance in Actinomycete Bacteria |
| title_short | Iron-Induced Respiration Promotes Antibiotic Resistance in Actinomycete Bacteria |
| title_sort | iron induced respiration promotes antibiotic resistance in actinomycete bacteria |
| topic | Streptomyces antibiotic resistance bactericidal antibiotic iron-induced respiration actinomycetes iron |
| url | https://journals.asm.org/doi/10.1128/mbio.00425-22 |
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