Sulfonamide resistance, virulence traits, and in-silico target interactions among clinical isolates in Setif, Algeria (2021–2023)
-
Anfal Kara
,
Imane Krache
,
Naouel Boussoualim
,
Roufaida Bourouche
,
Naouel Hamani
,
Malek Nour Kheloufi
,
Yacine Benguerba
Abstract
Background and Objectives: Antibiotic-resistant bacteria are a growing global health concern, particularly in developing regions. Sulfonamides, once widely used, now face increasing resistance. This study assessed the prevalence, resistance profiles, and virulences traites of sulfonamide-resistant strains in Sétif, Algeria (2021-2023).
Materials and Methods: A total of 215 clinical isolates were collected from patients aged 1 day to 96 years (mean 42.7). Most were community-acquired (77.2%), with urinary tract infections predominating (49.3% in women, 32.1% in men). Identification and susceptibility testing followed standard microbiological and Kirby–Bauer methods. Virulence factors (biofilm, hemolysin, protease, lecithinase, and lipase) were examined. Molecular docking compared sulfamethoxazole and trimethoprim binding to their enzymatic targets.
Results: Escherichia coli was the most frequent isolate (47.9%), followed by Enterobacter spp. (11.6%). Biofilm formation was common (88.8%), with complete production in Klebsiella, Citrobacter, Providencia, and Acinetobacter. Hemolysis patterns were α (30.7%), β (27.9%), and none (41.4%). Enzymatic activity included protease (48.8%), lecithinase (22.8%), and lipase (9.8%). High resistance was observed to penicillins (87.9%), cephalosporins (63.7%), and fluoroquinolones (56.3%). Resistance was lower to imipenem (33.0%) and amikacin (14.4%). Docking showed weaker sulfamethoxazole binding to DHPS than trimethoprim to DHFR.
Conclusion: The high prevalence of multidrug-resistant bacteria, especially E. coli, combined with biofilm and enzyme production, underscores the urgent need for careful antibiotic stewardship in this region.
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20. Kwok M, McGeorge S, Mayer-Coverdale J, Graves B, Paterson DL, Harris PNA, et al. Guideline of guidelines: management of recurrent urinary tract infections in women. BJU Int 2022; 130 Suppl 3(Suppl 3): 11-22.
21. Droupy S. L’hyperplasie bénigne de la prostate. Sexologies 2014; 23: 78-84.
22. Azab K, Abdel-Rahman MA, El-Sheikh HH, Farag MMS. Prevalence and relation of urinary tract infection bacterial pathogens to sex and ages among patients in three Arab countries. Al-Azhar J Pharm Sci 2021; 63: 194-206.
23. Tullus K, Shaikh N. Urinary tract infections in children. Lancet 2020; 395: 1659-1668.
24. Rodriguez-Mañas L. Urinary tract infections in the elderly: a review of disease characteristics and current treatment options. Drugs Context 2020; 9: 2020-4-13.
25. Islam MA, Islam MR, Khan R, Amin MB, Rahman M, Hossain MI, et al. Prevalence, etiology and antibiotic resistance patterns of community-acquired urinary tract infections in Dhaka, Bangladesh. PLoS One 2022; 17(9): e0274423.
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27. Kiiru S, Maina J, Katana J, Mwaniki J, Asiimwe BB, Mshana SE, et al. Bacterial etiology of urinary tract infections in patients treated at Kenyan health facilities and their resistance towards commonly used antibiotics. PLoS One 2023; 18(5): e0277279.
28. Raoofi S, Pashazadeh Kan F, Rafiei S, Hosseinipalangi Z, Mejareh ZN, Khani S, et al. Global prevalence of nosocomial infection: a systematic review and meta-analysis. PLoS One 2023; 18(1): e0274248.
29. Svebrant S, Spörndly R, Lindberg RH, Sköldstam T, Larsson J, Öhagen P, et al. On-site pilot testing of hospital wastewater ozonation to reduce pharmaceutical residues and antibiotic-resistant bacteria. Antibiotics (Basel) 2021; 10: 684.
30. Garousi M, Monazami Tabar S, Mirazi H, Asgari P, Sabeghi P, Salehi A, et al. A global systematic review and meta-analysis on correlation between biofilm producers and non-biofilm producers with antibiotic resistance in uropathogenic Escherichia coli. Microb Pathog 2022; 164: 105412.
31. Boroumand M, Sharifi A, Ghatei MA, Sadrinasab M. Evaluation of biofilm formation and virulence genes and association with antibiotic resistance patterns of uropathogenic Escherichia coli strains in southwestern Iran. Jundishapur J Microbiol 2021; 14(9): e117785.
32. Joshi PA, Rajmane A, Shikhare V, Ramteerthakar M, Kulkarni V. A study of biofilm production and antimicrobial susceptibility pattern among urinary isolates. Indian J Microbiol Res 2021; 8: 268-273.
33. Arafa SH, Alshehri WA, Organji SR, Elbanna K, Obaid NA, Aldosari MS, et al. antimicrobial resistance, virulence factor-encoding genes, and biofilm-forming ability of community-associated uropathogenic Escherichia coli in western Saudi Arabia. Pol J Microbiol 2022; 71: 325-339.
34. Hiremath MB, Lava R. Study of virulence factors and antibiotic susceptibility pattern of extraintestinal pathogenic Escherichia coli. Indian J Microbiol Res 2020; 7: 330-334.
35. Verma V, Kumar P, Gupta S, Yadav S, Dhanda RS, Thorlacius H, et al. α-Hemolysin of uropathogenic E. coli regulates NLRP3 inflammasome activation and mitochondrial dysfunction in THP-1 macrophages. Sci Rep 2020; 10: 12653.
36. Ristow LC, Welch RA. Hemolysin of uropathogenic Escherichia coli: a cloak or a dagger? Biochim Biophys Acta 2016; 1858: 538-545.
37. Razzaq S, Dilshad R, Batool R, Jamil N. Diversity of industrially important hydrolytic enzymes explored in bacteria from aquatic environment. Pol J Nat Sci 2022; 37: 365-380.
38. Abdelaziz AA, Abo-Kamar AM, Elkotb ES, Al-Madboly LA. Microbial lipases: advances in production, purification, biochemical characterization, and multifaceted applications in industry and medicine. Microb Cell Fact 2025; 24: 40.
39. Benmoumou S, Hamaidi-Chergui F, Bouznada K, Bouras N, Bakli M, Meklat A. Antibiotic resistance pattern of Enterobacteriaceae strains isolated from community urinary tract infections in Algiers, Algeria. Adv Res Life Sci 2023; 7: 46-53.
40. Benamrouche N, Guettou B, Henniche FZ, Assaous F, Laouar H, Ziane H, et al. Vancomycin-resistant Enterococcus faecium in Algeria: phenotypic and genotypic characterization of clinical isolates. J Infect Dev Ctries 2021; 15: 95-101.
41. Tsopmene UJ, Iwewe YS, Eyong IM, Bisso BN, Dzoyem JP. Antibiotic resistance profile, biofilm formation ability, and virulence factors analysis of three Staphylococcus spp. isolates from urine. Cureus 2023; 15(4): e37877.
42. Jorba M, Pedrola M, Ghashghaei O, Herráez R, Campos-Vicens L, Luque FJ, et al. New trimethoprim-like molecules: bacteriological evaluation and insights into their action. Antibiotics (Basel) 2021; 10: 709.
43. Salem ME, Abdelhamid IA, Elwahy AHM, Ragheb MA, Alqahtani AS, Zaki MEA, et al. Novel hybrid thiazoles, bis-thiazoles linked to azo-sulfamethoxazole: synthesis, docking, and antimicrobial activity. Heliyon 2024; 10(10): e31082.
2. Dhole S, Mahakalkar C, Kshirsagar S, Bhargava A. Antibiotic prophylaxis in surgery: current insights and future directions for surgical site infection prevention. Cureus 2023; 15(10): e47858.
3. Salam MA, Al-Amin MY, Salam MT, Pawar JS, Akhter N, Rabaan AA, et al. antimicrobial resistance: a growing serious threat for global public health. Healthcare (Basel) 2023; 11: 1946.
4. Zalewska M, Błażejewska A, Czapko A, Popowska M. Antibiotics and antibiotic resistance genes in animal manure – consequences of its application in agriculture. Front Microbiol 2021; 12: 610656.
5. Sköld O. Sulfonamide resistance: mechanisms and trends. Drug Resist Updat 2000; 3: 155-160.
6. Hudzicki J (2009). Kirby-Bauer Disk Diffusion Susceptibility Test Protocol. American Society for Microbiology.
https://www.scirp.org/reference/referencespapers?referenceid=2965547
7. O’Toole GA. Microtiter dish biofilm formation assay. J Vis Exp 2011; (47): 2437.
8. Stepanović S, Vuković D, Hola V, Di Bonaventura G, Djukić S, Cirković I, et al. Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations. APMIS 2007; 115: 891-899.
9. Türkel İ, Yıldırım T, Yazgan B, Bilgin M, Başbulut E. Relationship between antibiotic resistance, efflux pumps, and biofilm formation in ESBL-producing Klebsiella pneumoniae. J Chemother 2018; 30: 354-363.
10. Mogrovejo-Arias DC, Brill FHH, Wagner D. Potentially pathogenic bacteria isolated from diverse habitats in Spitsbergen, Svalbard. Environ Earth Sci 2020; 79: 109.
11. Tula MY, Filgona J, Kyauta SE, Elisha R. Screening for some virulent factors among bacterial isolates from surfaces of hospital fomites and hands of healthcare workers. Cell Mol Biomed Rep 2023; 3: 9-16.
12. Riffel A, Brandelli A. Keratinolytic bacteria isolated from feather waste. Braz J Microbiol 2006; 37: 395-399.
13. AlDoori IHA, Mahal JD, Maaroof MN. Determination of genes responsible for some virulence factors of bacteria isolated from contaminated groundwater. Eurasia J Biosci 2020; 10: 4207-4215.
14. Korb O, Stützle T, Exner TE. Empirical scoring functions for advanced protein−ligand docking with PLANTS. J Chem Inf Model 2009; 49: 84-96.
15. Makhlouf Y, Bouaziz A, Benyahlou ZD, Boussebaa W, Benazi N, Yahiaoui S, et al. LC-MS/MS analysis, in vitro, in vivo and in silico anti-inflammatory evaluation of Anabasis articulata (Forssk.) Moq. extracts. Cellulose Chem Technol 2024; 58: 1099-1112.
16. Alhazmi AH, Alameer KM, Abuageelah BM, Alharbi RH, Mobarki M, Musawi S, et al. Epidemiology and antimicrobial resistance patterns of urinary tract infections: a cross-sectional study from Southwestern Saudi Arabia. Medicina (Kaunas) 2023; 59: 1411.
17. Aslam S, Albo M, Brubaker L. Recurrent urinary tract infections in adult women. JAMA 2020; 323: 658-659.
18. Czajkowski K, Broś-Konopielko M, Teliga-Czajkowska J. Urinary tract infection in women. Prz Menopauzalny 2021; 20: 40-47.
19. Nzalie RNT, Gonsu HK, Koulla-Shiro S. Bacterial etiology and antibiotic resistance profile of community-acquired urinary tract infections in a Cameroonian city. Int J Microbiol 2016; 2016: 3240268.
20. Kwok M, McGeorge S, Mayer-Coverdale J, Graves B, Paterson DL, Harris PNA, et al. Guideline of guidelines: management of recurrent urinary tract infections in women. BJU Int 2022; 130 Suppl 3(Suppl 3): 11-22.
21. Droupy S. L’hyperplasie bénigne de la prostate. Sexologies 2014; 23: 78-84.
22. Azab K, Abdel-Rahman MA, El-Sheikh HH, Farag MMS. Prevalence and relation of urinary tract infection bacterial pathogens to sex and ages among patients in three Arab countries. Al-Azhar J Pharm Sci 2021; 63: 194-206.
23. Tullus K, Shaikh N. Urinary tract infections in children. Lancet 2020; 395: 1659-1668.
24. Rodriguez-Mañas L. Urinary tract infections in the elderly: a review of disease characteristics and current treatment options. Drugs Context 2020; 9: 2020-4-13.
25. Islam MA, Islam MR, Khan R, Amin MB, Rahman M, Hossain MI, et al. Prevalence, etiology and antibiotic resistance patterns of community-acquired urinary tract infections in Dhaka, Bangladesh. PLoS One 2022; 17(9): e0274423.
26. Mohsenzadeh M, Abtahi-Eivary SH, Pirouzi A, Khaledi A, Rahimi M. A systematic review and meta-analysis of urinary tract infection, frequency of IS elements and MDR isolates retrieved from adult patients. Gene Rep 2020; 20: 100707.
27. Kiiru S, Maina J, Katana J, Mwaniki J, Asiimwe BB, Mshana SE, et al. Bacterial etiology of urinary tract infections in patients treated at Kenyan health facilities and their resistance towards commonly used antibiotics. PLoS One 2023; 18(5): e0277279.
28. Raoofi S, Pashazadeh Kan F, Rafiei S, Hosseinipalangi Z, Mejareh ZN, Khani S, et al. Global prevalence of nosocomial infection: a systematic review and meta-analysis. PLoS One 2023; 18(1): e0274248.
29. Svebrant S, Spörndly R, Lindberg RH, Sköldstam T, Larsson J, Öhagen P, et al. On-site pilot testing of hospital wastewater ozonation to reduce pharmaceutical residues and antibiotic-resistant bacteria. Antibiotics (Basel) 2021; 10: 684.
30. Garousi M, Monazami Tabar S, Mirazi H, Asgari P, Sabeghi P, Salehi A, et al. A global systematic review and meta-analysis on correlation between biofilm producers and non-biofilm producers with antibiotic resistance in uropathogenic Escherichia coli. Microb Pathog 2022; 164: 105412.
31. Boroumand M, Sharifi A, Ghatei MA, Sadrinasab M. Evaluation of biofilm formation and virulence genes and association with antibiotic resistance patterns of uropathogenic Escherichia coli strains in southwestern Iran. Jundishapur J Microbiol 2021; 14(9): e117785.
32. Joshi PA, Rajmane A, Shikhare V, Ramteerthakar M, Kulkarni V. A study of biofilm production and antimicrobial susceptibility pattern among urinary isolates. Indian J Microbiol Res 2021; 8: 268-273.
33. Arafa SH, Alshehri WA, Organji SR, Elbanna K, Obaid NA, Aldosari MS, et al. antimicrobial resistance, virulence factor-encoding genes, and biofilm-forming ability of community-associated uropathogenic Escherichia coli in western Saudi Arabia. Pol J Microbiol 2022; 71: 325-339.
34. Hiremath MB, Lava R. Study of virulence factors and antibiotic susceptibility pattern of extraintestinal pathogenic Escherichia coli. Indian J Microbiol Res 2020; 7: 330-334.
35. Verma V, Kumar P, Gupta S, Yadav S, Dhanda RS, Thorlacius H, et al. α-Hemolysin of uropathogenic E. coli regulates NLRP3 inflammasome activation and mitochondrial dysfunction in THP-1 macrophages. Sci Rep 2020; 10: 12653.
36. Ristow LC, Welch RA. Hemolysin of uropathogenic Escherichia coli: a cloak or a dagger? Biochim Biophys Acta 2016; 1858: 538-545.
37. Razzaq S, Dilshad R, Batool R, Jamil N. Diversity of industrially important hydrolytic enzymes explored in bacteria from aquatic environment. Pol J Nat Sci 2022; 37: 365-380.
38. Abdelaziz AA, Abo-Kamar AM, Elkotb ES, Al-Madboly LA. Microbial lipases: advances in production, purification, biochemical characterization, and multifaceted applications in industry and medicine. Microb Cell Fact 2025; 24: 40.
39. Benmoumou S, Hamaidi-Chergui F, Bouznada K, Bouras N, Bakli M, Meklat A. Antibiotic resistance pattern of Enterobacteriaceae strains isolated from community urinary tract infections in Algiers, Algeria. Adv Res Life Sci 2023; 7: 46-53.
40. Benamrouche N, Guettou B, Henniche FZ, Assaous F, Laouar H, Ziane H, et al. Vancomycin-resistant Enterococcus faecium in Algeria: phenotypic and genotypic characterization of clinical isolates. J Infect Dev Ctries 2021; 15: 95-101.
41. Tsopmene UJ, Iwewe YS, Eyong IM, Bisso BN, Dzoyem JP. Antibiotic resistance profile, biofilm formation ability, and virulence factors analysis of three Staphylococcus spp. isolates from urine. Cureus 2023; 15(4): e37877.
42. Jorba M, Pedrola M, Ghashghaei O, Herráez R, Campos-Vicens L, Luque FJ, et al. New trimethoprim-like molecules: bacteriological evaluation and insights into their action. Antibiotics (Basel) 2021; 10: 709.
43. Salem ME, Abdelhamid IA, Elwahy AHM, Ragheb MA, Alqahtani AS, Zaki MEA, et al. Novel hybrid thiazoles, bis-thiazoles linked to azo-sulfamethoxazole: synthesis, docking, and antimicrobial activity. Heliyon 2024; 10(10): e31082.
| Files | ||
| Issue | Vol 17 No 6 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v17i6.20370 | |
| Keywords | ||
| Drug resistance Sulfonamides Anti-bacterial agents Virulence factors Molecular docking simulation | ||
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How to Cite
1.
Kara A, Krache I, Boussoualim N, Bourouche R, Hamani N, Nour Kheloufi M, Benguerba Y. Sulfonamide resistance, virulence traits, and in-silico target interactions among clinical isolates in Setif, Algeria (2021–2023). Iran J Microbiol. 2025;17(6):1010-1022.
