Pitruzzello Giampaolo, Baumann Christoph G, Johnson Steven, Krauss Thomas F
Department of Physics University of York York YO10 5DD UK.
Department of Biology University of York York YO10 5DD UK.
Small Sci. 2022 Mar 24;2(5):2100123. doi: 10.1002/smsc.202100123. eCollection 2022 May.
Heterogeneous bacterial populations can display increased resistance to external threats, such as exposure to antibiotics. Despite the mounting clinical evidence supporting the importance of bacterial heterogeneity in acute infections, current antimicrobial susceptibility tests (ASTs) are typically insensitive to cell-to-cell differences as they only measure population-wide averages. Herein, the use of single-cell motility to address this issue is demonstrated. It is shown for the first time that antibiotic susceptibility detected as a change in single-cell motility is an excellent proxy for polyclonal and monoclonal heteroresistance. It is also demonstrated that motility and growth are both inhibited by an antibiotic with strikingly similar patterns, thus enabling the quantification of minimum inhibitory concentration (MIC) using a high-throughput, single-cell motility assay. The method allows for the detection of heteroresistance in and in 2 h or less and quantifies the MIC of an antibiotic in 1.5 h. The findings emphasize the need for characterizing bacterial heterogeneity, and they highlight the importance of single-cell bacterial motility in assessing both antibiotic susceptibility and population-wide heteroresistance.
异质细菌群体对外部威胁（如接触抗生素）可能表现出更强的抵抗力。尽管越来越多的临床证据支持细菌异质性在急性感染中的重要性，但目前的抗菌药物敏感性试验（AST）通常对细胞间差异不敏感，因为它们只测量群体平均值。本文展示了利用单细胞运动性来解决这一问题。首次表明，将抗生素敏感性检测为单细胞运动性的变化是多克隆和单克隆异质性耐药的良好指标。还证明了运动性和生长均受到抗生素的抑制，且模式极为相似，从而能够使用高通量单细胞运动性测定法对最低抑菌浓度（MIC）进行定量。该方法能够在2小时或更短时间内检测出异质性耐药，并在1.5小时内定量抗生素的MIC。这些发现强调了表征细菌异质性的必要性，并突出了单细胞细菌运动性在评估抗生素敏感性和群体异质性耐药方面的重要性。
