Investigation of the Effects of Non-Lethal Antibiotic Doses on Aeromonas veronii

Yıl 2024, Cilt: 7 Sayı: 6, 1148 - 1154, 15.11.2024

Berfin Eroğlu , Eda Delik , Burcu Emine Tefon Öztürk

https://doi.org/10.34248/bsengineering.1537803

Öz

Antibiotics are widely used pharmaceutical agents for the treatment of bacterial diseases in general. However, in recent years, the uncontrolled and incorrect use of antibiotics has led to bacteria being exposed to non-lethal sub-minimum inhibitory concentrations (sub-MIC) in various environments. This situation is critically important for understanding the effects of antibiotics on bacterial virulence factors. Antibiotics at sub-MICs affect bacterial virulence and resistance mechanisms, necessitating a revaluation of infection control and treatment strategies. In this study, the antimicrobial susceptibility of Aeromonas veronii isolate, isolated from a freshwater source, to antibiotics commonly used in clinical practice was evaluated, and MICs were determined for the antibiotics to which it was sensitive. Additionally, the effects of sub-MIC (MIC/2 and MIC/4) doses of antibiotics on the bacterium's biofilm formation capacity and morphology were investigated. The results revealed that A. veronii was resistant to 4 out of 14 antibiotics tested in the study (ampicillin, ceftazidime, ceftriaxone, and trimethoprim-sulfamethoxazole). Furthermore, sub-MICs were observed to reduce biofilm formation, with ciprofloxacin causing long filamentous morphology and meropenem resulting in a round cell morphology. These findings shed light on the effects of sub-MIC antibiotics on bacterial virulence and morphological characteristics and emphasize that these effects should be considered in clinical and environmental antibiotic management. Such studies are of great importance in preventing antibiotic resistance and developing treatment strategies.

Anahtar Kelimeler

Aeromonas veronii, Antibiotics, Bacterial morphology, Biofilm, Sub-MIC

Ölümcül Olmayan Antibiyotik Dozlarının Aeromonas veronii Üzerindeki Etkilerinin Araştırılması

Öz

Antibiyotikler, genellikle bakteriyel hastalıkların tedavisinde geniş çapta kullanılan farmasötik ajanlardır. Ancak, son yıllarda antibiyotiklerin kontrolsüz ve yanlış kullanımı, bakterilerin birçok farklı ortamda öldürücü olmayan sub-minimum inhibisyon konsantrasyonlarına (sub-MİK) maruz kalmasına neden olmuştur. Bu durum, antibiyotiklerin bakterilerin virülans faktörleri üzerindeki etkilerini anlamak açısından kritik bir önem taşımaktadır. Sub-MİK seviyelerdeki antibiyotikler, bakteriyel virülans ve direnç mekanizmalarını etkileyerek, enfeksiyon kontrolü ve tedavi stratejilerini yeniden değerlendirmeyi gerektirir. Bu çalışmada, bir tatlı su kaynağından izole edilen Aeromonas veronii izolatının klinikte yaygın olarak kullanılan antibiyotiklere karşı antimikrobiyal duyarlılığı değerlendirilmiş ve duyarlı olduğu antibiyotikler için MİK değerleri belirlenmiştir. Ayrıca, antibiyotiklerin sub-MİK (MİK/2 ve MİK/4) dozlarının bakterinin biyofilm oluşturma kapasitesiyle morfolojisi üzerindeki etkileri incelenmiştir. Sonuçlar, A. veronii’nin çalışmada kullanılan 14 antibiyotikten 4'üne (ampisilin, seftazidim, seftriakson ve trimetoprim-sülfametoksazol) direnç gösterdiğini ortaya koymuştur. Ayrıca sub-MİK'lerin biyofilm oluşumunu azalttığı, siprofloksasinin uzun filamentli, meropenemin ise yuvarlak hücre morfolojisine neden olduğu gözlemlenmiştir. Bu bulgular, antibiyotiklerin sub-MİK’lerinin bakteriyel virülans ve morfolojik özellikler üzerindeki etkilerini aydınlatmakta ve bu etkilerin klinik ve çevresel antibiyotik yönetiminde göz önünde bulundurulması gerektiğini vurgulamaktadır. Bu tür çalışmalar, antibiyotik direncinin önlenmesi ve tedavi stratejilerinin geliştirilmesi açısından büyük önem taşımaktadır.

Anahtar Kelimeler

Aeromonas veronii, Antibiyotik, Bakteriyel morfoloji, Biyofilm, Sub-MİK

Kaynakça

• Alhazmi MI. 2015. Isolation of Aeromonas spp. from food products: emerging Aeromonas infections and their significance in public health. J AOAC Int, 98(4): 927-929.
• Chadha J, Khullar L. 2021. Subinhibitory concentrations of nalidixic acid alter bacterial physiology and induce anthropogenic resistance in a commensal strain of Escherichia coli in vitro. Lett Appl Microbiol, 73(5): 623-633.
• Chen J, Zhou H, Huang J, Zhang R, Rao X. 2021. Virulence alterations in Staphylococcus aureus upon treatment with the sub-inhibitory concentrations of antibiotics. J Adv Res, 31: 165-175.
• CLSI, 2021. Performance Standards for Antimicrobial Susceptibility Testing. CLSI supplement M100 2021.
• Delik E, Eroğlu B, Tefon-Öztürk BE. 2024. Evaluation of the in vitro effects of concentrations of antibiotics on three Enterobacteriaceae isolates. World J Microbiol Biotechnol, 40(2): 1-16.
• Delik E, Eroğlu B, Çolak ÇY, Özçelik AT, Öztürk BET. 2023. Alterations of Growth, Biofilm-Forming, and Gene Expression of Bordetella pertussis by Antibiotics at Sub-Minimal Inhibitory Concentrations. Res Microbiol, 2023: 104058.
• Dhabaan GN, AbuBakar S, Cerqueira GM, Al-Haroni M, Pang SP, Hassan H. 2016. Imipenem treatment induces expression of important genes and phenotypes in a resistant Acinetobacter baumannii isolate. Antimicrob Agents Chemother, 60(3): 1370-1376.
• Dias C, Borges A, Saavedra MJ, Simões M. 2018. Biofilm formation and multidrug-resistant Aeromonas spp. from wild animals. J Glob Antimicrob Resist, 12: 227-234.
• Eden PA, Schmidt TM, Blakemore RP, Pace NR. 1991. Phylogenetic analysis of Aquaspirillum magnetotacticum using polymerase chain reaction-amplified 16S rRNA-specific DNA. Int J Syst Evol Microbiol, 41(2): 324-325.
• Eid HM, El-Mahallawy HS, Shalaby AM, Elsheshtawy HM, Shetewy MM, Eidaroos NH. 2022. Emergence of extensively drug-resistant Aeromonas hydrophila complex isolated from wild Mugil cephalus (striped mullet) and Mediterranean seawater. Vet World, 15(1): 55.
• Ghenghesh KS, Ahmed SF, El-Khalek RA, Al-Gendy A, Klena J. 2008. Aeromonas associated infections in developing countries. J Infect Dev Ctries, 2: 81–9.
• Gomes S, Fernandes C, Monteiro S, Cabecinha E, Teixeira A, Varandas S, Saavedra MJ. 2021. The role of aquatic ecosystems (River Tua, Portugal) as reservoirs of multidrug-resistant Aeromonas spp. Water, 13(5): 698.
• Janda JM, Abbott SL. 2010. The genus Aeromonas: taxonomy, pathogenicity, and infection. Clin Microbiol Rev, 23(1): 35-73.
• Lebeaux D, Ghigo JM, Beloin C. 2014. Biofilm-related infections: bridging the gap between clinical management and fundamental aspects of recalcitrance toward antibiotics. Microbiol Mol Biol, 78(3): 510-543.
• Lewis KIM. 2001. Riddle of biofilm resistance. Antimicrob Agents Chemother, 45(4): 999-1007.
• Li F, Wang W, Zhu Z, Chen A, Du P, Wang R, Wang D. 2015. Distribution, virulence-associated genes and antimicrobial resistance of Aeromonas isolates from diarrheal patients and water. China. J Infect, 70(6): 600-608.
• Lin TY, Santos TM, Kontur WS, Donohue TJ, Weibel DB. 2015. A cardiolipin-deficient mutant of Rhodobacter sphaeroides has an altered cell shape and is impaired in biofilm formation. J Bacteriol, 197(21): 3446-3455.
• Liu B, Zhang X, Ding X, Wang Y, Zhu G. 2021. Regulatory mechanisms of sub-inhibitory levels antibiotics agent in bacterial virulence. Appl Microbiol Biotechnol, 105(9): 3495-3505.
• Narimisa N, Amraei F, Kalani BS, Mohammadzadeh R, Jazi FM. 2020. Effects of sub-inhibitory concentrations of antibiotics and oxidative stress on the expression of type II toxin-antitoxin system genes in Klebsiella pneumoniae. J Glob Antimicrob Resist, 21: 51-56.
• Opstrup KV, Christiansen G, Birkelund S. 2023. Beta-lactam induced morphological changes in serum of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae blood isolates. Microbes Infect, 25(1-2): 105036.
• Pereira CS, Amorim SD, Santos AFDM, Siciliano S, Moreno IB, Ott PH, Rodrigues DDP. 2008. Plesiomonas shigelloides and Aeromonadaceae family pathogens isolated from marine mammals of Southern and Southeastern Brazilian coast. Braz J Microbiol, 39: 749-755.
• Persat A, Stone HA, Gitai Z. 2014. The curved shape of Caulobacter crescentus enhances surface colonization in flow. Nat Commun, 5(1): 3824.
• Pessoa RBG, de Oliveira WF, Marques DSC, dos Santos Correia MT, de Carvalho EVMM, Coelho LCBB. 2019. The genus Aeromonas: A general approach. Microb Pathog, 130: 81-94.
• Rowlett VW, Mallampalli VK, Karlstaedt A, Dowhan W, Taegtmeyer H, Margolin W, Vitrac H. 2017. Impact of membrane phospholipid alterations in Escherichia coli on cellular function and bacterial stress adaptation. J Bacteriol, 199(13): 10-1128.
• Salama NR. 2020. Cell morphology as a virulence determinant: lessons from Helicobacter pylori. Curr Opin Microbiol, 54, 11-17.
• Tang M, Wei X, Wan X, Ding Z, Ding Y, Liu J. 2020. The role and relationship with efflux pump of biofilm formation in Klebsiella pneumoniae. Microb Pathog, 147:104244.
• Woo SJ, Kim MS, Jeong MG, Do MY, Hwang SD, Kim WJ. 2022. Establishment of epidemiological cut-off values and the distribution of resistance genes in Aeromonas hydrophila and Aeromonas veronii isolated from aquatic animals. Antibiotics, 11(3): 343.
• Yuwono C, Wehrhahn MC, Liu F, Riordan SM, Zhang L. 2021. The Isolation of Aeromonas Species and Other Common Enteric Bacterial Pathogens from Patients with Gastroenteritis in an Australian Population. Microorganisms, 9(7): 1440.