Hintzen Kim F H, Blanchet Lionel, Smolinska Agnieszka, Boumans Marie-Louise, Stobberingh Ellen E, Dallinga Jan W, Lubbers Tim, van Schooten Frederik-Jan, Boots Agnes W
Department of Pharmacology and Toxicology, Maastricht University, Maastricht, The Netherlands.
Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
PLoS One. 2024 Jan 26;19(1):e0297086. doi: 10.1371/journal.pone.0297086. eCollection 2024.
Early and reliable determination of bacterial strain specificity and antibiotic resistance is critical to improve sepsis treatment. Previous research demonstrated the potential of headspace analysis of volatile organic compounds (VOCs) to differentiate between various microorganisms associated with pulmonary infections in vitro. This study evaluates whether VOC analysis can also discriminate antibiotic sensitive from resistant bacterial strains when cultured on varying growth media.
Both antibiotic-sensitive and -resistant strains of Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumonia were cultured on 4 different growth media, i.e. Brain Heart Infusion, Marine Broth, Müller-Hinton and Trypticase Soy Agar. After overnight incubation at 37°C, the headspace air of the cultures was collected on stainless steel desorption tubes and analyzed by gas chromatography time-of-flight mass spectrometry (GC-tof-MS). Statistical analysis was performed using regularized multivariate analysis of variance and cross validation.
The three bacterial species could be correctly recognized based on the differential presence of 14 VOCs (p<0.001). This discrimination was not influenced by the different growth media. Interestingly, a clear discrimination could be made between the antibiotic-resistant and -sensitive variant of Pseudomonas aeruginosa (p<0.001) based on their species-specific VOC signature.
This study demonstrates that isolated microorganisms, including antibiotic-sensitive and -resistant strains of Pseudomonas aeruginosa, could be identified based on their excreted VOCs independent of the applied growth media. These findings suggest that the discriminating volatiles are associated with the microorganisms themselves rather than with their growth medium. This study exemplifies the potential of VOC analysis as diagnostic tool in medical microbiology. However, validation of our results in appropriate in vivo models is critical to improve translation of breath analysis to clinical applications.
早期且可靠地确定细菌菌株特异性和抗生素耐药性对于改善脓毒症治疗至关重要。先前的研究表明,挥发性有机化合物(VOCs)的顶空分析在体外区分与肺部感染相关的各种微生物方面具有潜力。本研究评估了在不同生长培养基上培养时,VOC分析是否也能区分抗生素敏感和耐药细菌菌株。
铜绿假单胞菌、金黄色葡萄球菌和肺炎克雷伯菌的抗生素敏感和耐药菌株在4种不同的生长培养基上培养,即脑心浸液、海洋肉汤、穆勒-欣顿培养基和胰蛋白胨大豆琼脂。在37°C过夜培养后,将培养物的顶空气体收集在不锈钢解吸管上,并通过气相色谱飞行时间质谱(GC-tof-MS)进行分析。使用正则化多变量方差分析和交叉验证进行统计分析。
基于14种VOCs的差异存在(p<0.001),可以正确识别这三种细菌物种。这种区分不受不同生长培养基的影响。有趣的是,基于其物种特异性VOC特征,可以在铜绿假单胞菌的抗生素耐药和敏感变体之间做出明确区分(p<0.001)。
本研究表明,包括铜绿假单胞菌的抗生素敏感和耐药菌株在内的分离微生物,可以根据其分泌的VOCs进行识别,而与所使用的生长培养基无关。这些发现表明,具有区分作用的挥发物与微生物本身相关,而非与其生长培养基相关。本研究例证了VOC分析作为医学微生物学诊断工具的潜力。然而,在适当的体内模型中验证我们的结果对于将呼吸分析转化为临床应用至关重要。