Combined mutations of the penA with ftsX genes contribute to ceftriaxone resistance in Neisseria gonorrhoeae and peptide nucleic acids targeting these genes reverse ceftriaxone resistance
ABSTRACT: Objectives: To investigate the gene mutations associated with ceftriaxone (CRO) resistance among gonococcal isolates, and to determine the effects of the mutated genes on CRO minimum inhibitory concentrations (MICs) with transformation assays and antisense peptide nucleic acids (asPNAs)....
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Journal of Global Antimicrobial Resistance |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213716523001297 |
| _version_ | 1797448770147844096 |
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| author | Lin Zhu Jingyao Liang Yue Zheng Shaochun Chen Qingfang Xu Songchao Yin Yiyong Hong Wenling Cao Wei Lai Zijian Gong |
| author_facet | Lin Zhu Jingyao Liang Yue Zheng Shaochun Chen Qingfang Xu Songchao Yin Yiyong Hong Wenling Cao Wei Lai Zijian Gong |
| author_sort | Lin Zhu |
| collection | DOAJ |
| description | ABSTRACT: Objectives: To investigate the gene mutations associated with ceftriaxone (CRO) resistance among gonococcal isolates, and to determine the effects of the mutated genes on CRO minimum inhibitory concentrations (MICs) with transformation assays and antisense peptide nucleic acids (asPNAs). Methods: Ceftriaxone-resistant (CROR) and ceftriaxone-susceptible (CROS) isolates were identified using EUCAST and paired according to similarity in their MICs to other antimicrobials. The two groups of gonococci were sequenced and analysed. Mutated genes that showed a statistical difference between the two groups were transformed into gonococcal reference strains to determine their functions. AsPNAs were designed and transformed into the former transformant to further confirm the effects of the mutated genes. Results: Twenty-two paired CROR and CROS isolates were obtained. The incidence of the penA-A501T and penA-G542S mutations individually, as well as combined mutations (penA-A501T and ftsX-R251H, penA-G542S and ftsX R251H), was statistically different between the two groups. The MIC of ATCC43069 (A43) increased 2 times following transformation with penA-A501T, and the MICs of A43 and ATCC49226 (A49) increased 32 times and 2 times following transformation with penA-A501T and ftsX-R251H, respectively. Antisense PNA-P3 reduced the MIC of the A43 transformant most significantly when transformed individually. PNA-P3 and PNA-F1 (asPNAs of the penA and ftsX) restored CRO susceptibility. Conclusions: PenA-A501T and penA-G542S mutations are important in CRO resistance among gonococci isolates. The ftsX-R251H mutation is also related to CRO resistance, and combined mutations of ftsX-R251H and penA-A501T comediate a significant reduction in CRO susceptibility. The combined application of PNA-P3 and PNA-F1 could effectively reverse the resistance to CRO in N. gonorrhoeae. |
| first_indexed | 2024-03-09T14:15:16Z |
| format | Article |
| id | doaj.art-ec29b2e13a2c45b2bde89201096e8583 |
| institution | Directory Open Access Journal |
| issn | 2213-7165 |
| language | English |
| last_indexed | 2024-03-09T14:15:16Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Global Antimicrobial Resistance |
| spelling | doaj.art-ec29b2e13a2c45b2bde89201096e85832023-11-29T04:24:20ZengElsevierJournal of Global Antimicrobial Resistance2213-71652023-12-01351925Combined mutations of the penA with ftsX genes contribute to ceftriaxone resistance in Neisseria gonorrhoeae and peptide nucleic acids targeting these genes reverse ceftriaxone resistanceLin Zhu0Jingyao Liang1Yue Zheng2Shaochun Chen3Qingfang Xu4Songchao Yin5Yiyong Hong6Wenling Cao7Wei Lai8Zijian Gong9Department of Dermato-Venereology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, ChinaDepartment of Dermato-Venereology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaInstitute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaDepartment of Dermato-Venereology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Dermato-Venereology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Dermato-Venereology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, ChinaDepartment of Dermato-Venereology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Dermato-Venereology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaABSTRACT: Objectives: To investigate the gene mutations associated with ceftriaxone (CRO) resistance among gonococcal isolates, and to determine the effects of the mutated genes on CRO minimum inhibitory concentrations (MICs) with transformation assays and antisense peptide nucleic acids (asPNAs). Methods: Ceftriaxone-resistant (CROR) and ceftriaxone-susceptible (CROS) isolates were identified using EUCAST and paired according to similarity in their MICs to other antimicrobials. The two groups of gonococci were sequenced and analysed. Mutated genes that showed a statistical difference between the two groups were transformed into gonococcal reference strains to determine their functions. AsPNAs were designed and transformed into the former transformant to further confirm the effects of the mutated genes. Results: Twenty-two paired CROR and CROS isolates were obtained. The incidence of the penA-A501T and penA-G542S mutations individually, as well as combined mutations (penA-A501T and ftsX-R251H, penA-G542S and ftsX R251H), was statistically different between the two groups. The MIC of ATCC43069 (A43) increased 2 times following transformation with penA-A501T, and the MICs of A43 and ATCC49226 (A49) increased 32 times and 2 times following transformation with penA-A501T and ftsX-R251H, respectively. Antisense PNA-P3 reduced the MIC of the A43 transformant most significantly when transformed individually. PNA-P3 and PNA-F1 (asPNAs of the penA and ftsX) restored CRO susceptibility. Conclusions: PenA-A501T and penA-G542S mutations are important in CRO resistance among gonococci isolates. The ftsX-R251H mutation is also related to CRO resistance, and combined mutations of ftsX-R251H and penA-A501T comediate a significant reduction in CRO susceptibility. The combined application of PNA-P3 and PNA-F1 could effectively reverse the resistance to CRO in N. gonorrhoeae.http://www.sciencedirect.com/science/article/pii/S2213716523001297ftsXpenANeisseria gonorrhoeaeceftriaxone resistanceantisense peptide nucleic acid |
| spellingShingle | Lin Zhu Jingyao Liang Yue Zheng Shaochun Chen Qingfang Xu Songchao Yin Yiyong Hong Wenling Cao Wei Lai Zijian Gong Combined mutations of the penA with ftsX genes contribute to ceftriaxone resistance in Neisseria gonorrhoeae and peptide nucleic acids targeting these genes reverse ceftriaxone resistance Journal of Global Antimicrobial Resistance ftsX penA Neisseria gonorrhoeae ceftriaxone resistance antisense peptide nucleic acid |
| title | Combined mutations of the penA with ftsX genes contribute to ceftriaxone resistance in Neisseria gonorrhoeae and peptide nucleic acids targeting these genes reverse ceftriaxone resistance |
| title_full | Combined mutations of the penA with ftsX genes contribute to ceftriaxone resistance in Neisseria gonorrhoeae and peptide nucleic acids targeting these genes reverse ceftriaxone resistance |
| title_fullStr | Combined mutations of the penA with ftsX genes contribute to ceftriaxone resistance in Neisseria gonorrhoeae and peptide nucleic acids targeting these genes reverse ceftriaxone resistance |
| title_full_unstemmed | Combined mutations of the penA with ftsX genes contribute to ceftriaxone resistance in Neisseria gonorrhoeae and peptide nucleic acids targeting these genes reverse ceftriaxone resistance |
| title_short | Combined mutations of the penA with ftsX genes contribute to ceftriaxone resistance in Neisseria gonorrhoeae and peptide nucleic acids targeting these genes reverse ceftriaxone resistance |
| title_sort | combined mutations of the pena with ftsx genes contribute to ceftriaxone resistance in neisseria gonorrhoeae and peptide nucleic acids targeting these genes reverse ceftriaxone resistance |
| topic | ftsX penA Neisseria gonorrhoeae ceftriaxone resistance antisense peptide nucleic acid |
| url | http://www.sciencedirect.com/science/article/pii/S2213716523001297 |
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