Article ; Online: Molecular mechanism of Hfq-dependent sRNA1039 and sRNA1600 regulating antibiotic resistance and virulence in Shigella sonnei.
International journal of antimicrobial agents
2023 Volume 63, Issue 2, Page(s) 107070
Abstract: Bacillary dysentery caused by Shigella spp. is a significant concern for human health. Small non-coding RNA (sRNA) plays a crucial role in regulating antibiotic resistance and virulence in Shigella spp. However, the specific mechanisms behind this ... ...
Abstract | Bacillary dysentery caused by Shigella spp. is a significant concern for human health. Small non-coding RNA (sRNA) plays a crucial role in regulating antibiotic resistance and virulence in Shigella spp. However, the specific mechanisms behind this phenomenon are still not fully understood. This study discovered two sRNAs (sRNA1039 and sRNA1600) that may be involved in bacterial resistance and virulence. By constructing deletion mutants (WT/ΔSR1039 and WT/ΔSR1600), this study found that the WT/ΔSR1039 mutants caused a two-fold increase in sensitivity to ampicillin, gentamicin and cefuroxime, and the WT/ΔSR1600 mutants caused a two-fold increase in sensitivity to cefuroxime. Furthermore, the WT/ΔSR1600 mutants caused a decrease in the adhesion and invasion of bacteria to HeLa cells (P<0.01), and changed the oxidative stress level of bacteria to reduce their survival rate (P<0.001). Subsequently, this study explored the molecular mechanisms by which sRNA1039 and sRNA1600 regulate antibiotic resistance and virulence. The deletion of sRNA1039 accelerated the degradation of target gene cfa mRNA and reduced its expression, thereby regulating the expression of pore protein gene ompD indirectly and negatively to increase bacterial sensitivity to ampicillin, gentamicin and cefuroxime. The inactivation of sRNA1600 reduced the formation of persister cells to reduce resistance to cefuroxime, and reduced the expression of type-III-secretion-system-related genes to reduce bacterial virulence by reducing the expression of target gene tomB. These results provide new insights into Hfq-sRNA-mRNA regulation of the resistance and virulence network of Shigella sonnei, which could potentially promote the development of more effective treatment strategies. |
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MeSH term(s) | Humans ; Shigella sonnei/genetics ; Virulence/genetics ; HeLa Cells ; Cefuroxime/metabolism ; Shigella flexneri/genetics ; Shigella ; Dysentery, Bacillary/microbiology ; Ampicillin/pharmacology ; Ampicillin/metabolism ; Drug Resistance, Microbial ; Gentamicins ; RNA, Messenger ; RNA, Small Untranslated/genetics ; RNA, Small Untranslated/metabolism ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/metabolism |
Chemical Substances | Cefuroxime (O1R9FJ93ED) ; Ampicillin (7C782967RD) ; Gentamicins ; RNA, Messenger ; RNA, Small Untranslated ; Anti-Bacterial Agents |
Language | English |
Publishing date | 2023-12-22 |
Publishing country | Netherlands |
Document type | Journal Article |
ZDB-ID | 1093977-5 |
ISSN | 1872-7913 ; 0924-8579 |
ISSN (online) | 1872-7913 |
ISSN | 0924-8579 |
DOI | 10.1016/j.ijantimicag.2023.107070 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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