TY - JOUR
T1 - AldB controls persister formation in Escherichia coli depending on environmental stress
AU - Kawai, Yuto
AU - Matsumoto, Shinya
AU - Ling, Yiwei
AU - Okuda, Shujiro
AU - Tsuneda, Satoshi
N1 - Publisher Copyright:
© 2018 The Societies and John Wiley & Sons Australia, Ltd
PY - 2018/5
Y1 - 2018/5
N2 - Persisters are multidrug-tolerant cells that are present within antibiotic-sensitive populations. Persister formation is not induced by genetic mutations, but rather by changes in the degree of expression of some genes. High redundancy has been observed among the pathways that have been hypothesized to respond to specific stresses. In this study, we conducted RNA sequencing of Escherichia coli persisters under various stress conditions to identify common mechanisms. We induced stresses such as glucose or amino acid exhaustion, acid stress and anaerobic conditions, all of which are encountered during bacterial pathogenesis. We found that most genes are differentially expressed depending on the specific stress condition; however, some genes were commonly expressed in persisters in most stress conditions. Commonly expressed genes are expected to be promising therapeutic targets for combating persistent infections. We found that knockdown of aldehyde dehydrogenase (aldB), which was expressed in every condition except for acid stress, decreased persisters in the non-stressed condition. However, the same strain unexpectedly showed an increased number of persisters in the amino acid-limited condition. Because the increase in persister number is glycolytic metabolite-dependent, metabolic flow may play a crucial role in aldB-mediated persister formation. These data suggest that environmental stresses alter persister mechanisms. Identification of environmental influences on persister formation during pathogenesis is therefore necessary to enabling persister eradication.
AB - Persisters are multidrug-tolerant cells that are present within antibiotic-sensitive populations. Persister formation is not induced by genetic mutations, but rather by changes in the degree of expression of some genes. High redundancy has been observed among the pathways that have been hypothesized to respond to specific stresses. In this study, we conducted RNA sequencing of Escherichia coli persisters under various stress conditions to identify common mechanisms. We induced stresses such as glucose or amino acid exhaustion, acid stress and anaerobic conditions, all of which are encountered during bacterial pathogenesis. We found that most genes are differentially expressed depending on the specific stress condition; however, some genes were commonly expressed in persisters in most stress conditions. Commonly expressed genes are expected to be promising therapeutic targets for combating persistent infections. We found that knockdown of aldehyde dehydrogenase (aldB), which was expressed in every condition except for acid stress, decreased persisters in the non-stressed condition. However, the same strain unexpectedly showed an increased number of persisters in the amino acid-limited condition. Because the increase in persister number is glycolytic metabolite-dependent, metabolic flow may play a crucial role in aldB-mediated persister formation. These data suggest that environmental stresses alter persister mechanisms. Identification of environmental influences on persister formation during pathogenesis is therefore necessary to enabling persister eradication.
KW - Escherichia coli
KW - RNA sequencing
KW - environmental stress
KW - persister
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U2 - 10.1111/1348-0421.12587
DO - 10.1111/1348-0421.12587
M3 - Article
C2 - 29577369
AN - SCOPUS:85045928300
SN - 0385-5600
VL - 62
SP - 299
EP - 309
JO - Microbiology and Immunology
JF - Microbiology and Immunology
IS - 5
ER -