The Characterization of a Gonococcal HicAB Toxin–Antitoxin System Capable of Causing Bacteriostatic Growth Arrest
<i>Neisseria gonorrhoeae</i> is the causative agent of the sexually transmitted infection gonorrhea. Preventative vaccines or novel treatments based on a better understanding of the molecular basis of <i>N. gonorrhoeae</i> infection are required as resistance to current antib...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
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| Series: | Microorganisms |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-2607/13/7/1619 |
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| Summary: | <i>Neisseria gonorrhoeae</i> is the causative agent of the sexually transmitted infection gonorrhea. Preventative vaccines or novel treatments based on a better understanding of the molecular basis of <i>N. gonorrhoeae</i> infection are required as resistance to current antibiotics is widespread. Toxin–antitoxin (TA) systems modulate bacterial physiology by interfering with vital cellular processes; type II TA systems, where both toxin and antitoxin are proteins, are the best-studied. Bioinformatics analysis revealed genes encoding an uncharacterized type II HicAB TA system in the <i>N. gonorrhoeae</i> strain FA1090 chromosome, which were also present in >83% of the other gonococcal genome sequences examined. Gonococcal HicA overproduction inhibited bacterial growth in <i>Escherichia coli,</i> an effect that could be counteracted by the co-expression of HicB. Kill/rescue assays showed that this effect was bacteriostatic rather than bactericidal. The site-directed mutagenesis of key histidine and glycine residues (Gly22, His24, His29) abolished HicA-mediated growth arrest. <i>N. gonorrhoeae</i> FA1090∆<i>hicAB</i> and complemented derivatives that expressed IPTG-inducible <i>hicA</i>, <i>hicB</i>, or <i>hicAB</i>, respectively, grew as wild type, except for IPTG-induced FA1090∆<i>hicAB::hicA.</i> RT-PCR demonstrated that <i>hicAB</i> are transcribed in vitro under the culture conditions used. The deletion of <i>hicAB</i> had no effect on biofilm formation. Our study describes the first characterization of a HicAB TA system in <i>N. gonorrhoeae</i>. |
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| ISSN: | 2076-2607 |