<i>Acinetobacter baumannii</i> under Acidic Conditions Induces Colistin Resistance through PmrAB Activation and Lipid A Modification
Colistin is a last-resort antimicrobial agent for treating carbapenem-resistant <i>Acinetobacter baumannii</i> infections. The activation of PmrAB by several environmental signals induces colistin resistance in Gram-negative bacteria. This study investigated the molecular mechanisms of c...
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MDPI AG
2023-04-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/12/5/813 |
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| author | Seo-Yeon Ko Nayeong Kim Seong-Yong Park Seong-Yeop Kim Minsang Shin Je-Chul Lee |
| author_facet | Seo-Yeon Ko Nayeong Kim Seong-Yong Park Seong-Yeop Kim Minsang Shin Je-Chul Lee |
| author_sort | Seo-Yeon Ko |
| collection | DOAJ |
| description | Colistin is a last-resort antimicrobial agent for treating carbapenem-resistant <i>Acinetobacter baumannii</i> infections. The activation of PmrAB by several environmental signals induces colistin resistance in Gram-negative bacteria. This study investigated the molecular mechanisms of colistin resistance in <i>A. baumannii</i> under acidic conditions using wild-type (WT) <i>A. baumannii</i> 17978, Δ<i>pmrA</i> and Δ<i>pmrB</i> mutants, and <i>pmrA</i>-complemented strains. The <i>pmrA</i> or <i>pmrB</i> deletion did not affect the growth of <i>A. baumannii</i> under acidic or aerobic conditions. <i>A. baumannii</i> under acidic (pH 5.5) and high-iron (1 mM) conditions showed 32- and 8-fold increases in the minimum inhibitory concentrations (MICs) of colistin, respectively. The Δ<i>pmrA</i> and Δ<i>pmrB</i> mutants at pH 5.5 showed a significant decrease in colistin MICs compared to the WT strain at pH 5.5. No difference in colistin MICs was observed between WT and mutant strains under high-iron conditions. The <i>pmrCAB</i> expression significantly increased in the WT strain at pH 5.5 compared to the WT strain at pH 7.0. The <i>pmrC</i> expression significantly decreased in two mutant strains at pH 5.5 compared to the WT strain at pH 5.5. The PmrA protein was expressed in the Δ<i>pmrA</i> strain carrying ppmrA_FLAG plasmids at pH 5.5 but not at pH 7.0. Lipid A modification by the addition of phosphoethanolamine was observed in the WT strain at pH 5.5. In conclusion, this study demonstrated that <i>A. baumannii</i> under acidic conditions induces colistin resistance via the activation of <i>pmrCAB</i> operon and subsequent lipid A modification. |
| first_indexed | 2024-03-11T04:01:00Z |
| format | Article |
| id | doaj.art-d234abfd173f4400839909033514421a |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-11T04:01:00Z |
| publishDate | 2023-04-01 |
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| series | Antibiotics |
| spelling | doaj.art-d234abfd173f4400839909033514421a2023-11-18T00:11:37ZengMDPI AGAntibiotics2079-63822023-04-0112581310.3390/antibiotics12050813<i>Acinetobacter baumannii</i> under Acidic Conditions Induces Colistin Resistance through PmrAB Activation and Lipid A ModificationSeo-Yeon Ko0Nayeong Kim1Seong-Yong Park2Seong-Yeop Kim3Minsang Shin4Je-Chul Lee5Department of Microbiology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of KoreaDepartment of Microbiology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of KoreaDepartment of Microbiology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of KoreaDepartment of Microbiology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of KoreaDepartment of Microbiology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of KoreaDepartment of Microbiology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of KoreaColistin is a last-resort antimicrobial agent for treating carbapenem-resistant <i>Acinetobacter baumannii</i> infections. The activation of PmrAB by several environmental signals induces colistin resistance in Gram-negative bacteria. This study investigated the molecular mechanisms of colistin resistance in <i>A. baumannii</i> under acidic conditions using wild-type (WT) <i>A. baumannii</i> 17978, Δ<i>pmrA</i> and Δ<i>pmrB</i> mutants, and <i>pmrA</i>-complemented strains. The <i>pmrA</i> or <i>pmrB</i> deletion did not affect the growth of <i>A. baumannii</i> under acidic or aerobic conditions. <i>A. baumannii</i> under acidic (pH 5.5) and high-iron (1 mM) conditions showed 32- and 8-fold increases in the minimum inhibitory concentrations (MICs) of colistin, respectively. The Δ<i>pmrA</i> and Δ<i>pmrB</i> mutants at pH 5.5 showed a significant decrease in colistin MICs compared to the WT strain at pH 5.5. No difference in colistin MICs was observed between WT and mutant strains under high-iron conditions. The <i>pmrCAB</i> expression significantly increased in the WT strain at pH 5.5 compared to the WT strain at pH 7.0. The <i>pmrC</i> expression significantly decreased in two mutant strains at pH 5.5 compared to the WT strain at pH 5.5. The PmrA protein was expressed in the Δ<i>pmrA</i> strain carrying ppmrA_FLAG plasmids at pH 5.5 but not at pH 7.0. Lipid A modification by the addition of phosphoethanolamine was observed in the WT strain at pH 5.5. In conclusion, this study demonstrated that <i>A. baumannii</i> under acidic conditions induces colistin resistance via the activation of <i>pmrCAB</i> operon and subsequent lipid A modification.https://www.mdpi.com/2079-6382/12/5/813PmrAB<i>Acinetobacter baumannii</i>lipopolysaccharidelipid Acolistin |
| spellingShingle | Seo-Yeon Ko Nayeong Kim Seong-Yong Park Seong-Yeop Kim Minsang Shin Je-Chul Lee <i>Acinetobacter baumannii</i> under Acidic Conditions Induces Colistin Resistance through PmrAB Activation and Lipid A Modification Antibiotics PmrAB <i>Acinetobacter baumannii</i> lipopolysaccharide lipid A colistin |
| title | <i>Acinetobacter baumannii</i> under Acidic Conditions Induces Colistin Resistance through PmrAB Activation and Lipid A Modification |
| title_full | <i>Acinetobacter baumannii</i> under Acidic Conditions Induces Colistin Resistance through PmrAB Activation and Lipid A Modification |
| title_fullStr | <i>Acinetobacter baumannii</i> under Acidic Conditions Induces Colistin Resistance through PmrAB Activation and Lipid A Modification |
| title_full_unstemmed | <i>Acinetobacter baumannii</i> under Acidic Conditions Induces Colistin Resistance through PmrAB Activation and Lipid A Modification |
| title_short | <i>Acinetobacter baumannii</i> under Acidic Conditions Induces Colistin Resistance through PmrAB Activation and Lipid A Modification |
| title_sort | i acinetobacter baumannii i under acidic conditions induces colistin resistance through pmrab activation and lipid a modification |
| topic | PmrAB <i>Acinetobacter baumannii</i> lipopolysaccharide lipid A colistin |
| url | https://www.mdpi.com/2079-6382/12/5/813 |
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