Seaman Paul F, Ochs Dietmar, Day Martin J
Cardiff School of Biosciences, Cardiff University, Park Place, Cardiff CF10 3TL, UK.
J Antimicrob Chemother. 2007 Jan;59(1):43-50. doi: 10.1093/jac/dkl450. Epub 2006 Oct 31.
A little-understood mode of antimicrobial resistance in Staphylococcus aureus is the evolution of a sub-population of small-colony variants (SCVs). SCVs are a cause of persistent and recurring infections refractory to antimicrobial chemotherapy. Following the inadvertent isolation of suspected SCVs growing in the presence of triclosan we set out to evaluate the formation of these colonial mutants and assess their antimicrobial susceptibility.
SCVs were isolated on Mueller-Hinton agar supplemented with 1 mg/L triclosan. SCV formation frequency was calculated using a selection of both clinical methicillin-resistant S. aureus (MRSA) isolates and methicillin-susceptible S. aureus strains. Antimicrobial susceptibility was assessed and the fabI gene of SCVs was sequenced to ensure resistance was not mediated by mutation of this gene.
We have found in vitro that triclosan can select for S. aureus colonies showing the characteristic SCV phenotype with low-level triclosan resistance and which coincidently have reduced susceptibility to penicillin and gentamicin. Additionally, triclosan-isolated SCVs were shown to have an increased tolerance to the lethal effects of triclosan.
We propose the formation of SCVs by S. aureus is a novel mechanism of resistance to low concentrations of triclosan, which for 25 years has been used widely in the domestic setting in various consumer healthcare products. More recently it has been recommended for the control of MRSA. Consequently, our results identify the potential for treatment failure in infections already notoriously difficult to eradicate. It remains unclear to what extent isolates with decreased susceptibility to triclosan would develop and have the fitness to survive under real world conditions.
金黄色葡萄球菌中一种鲜为人知的抗菌耐药模式是小菌落变体（SCV）亚群的进化。SCV是导致对抗菌化疗难治的持续性和复发性感染的原因。在无意中分离出在三氯生存在下生长的疑似SCV后，我们着手评估这些菌落突变体的形成并评估它们的抗菌敏感性。
在补充有1mg/L三氯生的穆勒-欣顿琼脂上分离SCV。使用多种临床耐甲氧西林金黄色葡萄球菌（MRSA）分离株和甲氧西林敏感金黄色葡萄球菌菌株计算SCV形成频率。评估抗菌敏感性并对SCV的fabI基因进行测序，以确保耐药性不是由该基因突变介导的。
我们在体外发现，三氯生可以选择出表现出特征性SCV表型的金黄色葡萄球菌菌落，这些菌落具有低水平的三氯生耐药性，并且巧合地对青霉素和庆大霉素的敏感性降低。此外，经三氯生分离的SCV对三氯生的致死作用具有更高的耐受性。
我们提出金黄色葡萄球菌形成SCV是对低浓度三氯生耐药的一种新机制，三氯生在25年来已广泛用于国内各种消费保健产品中。最近，它被推荐用于控制MRSA。因此，我们的结果表明在已经 notoriously难以根除的感染中存在治疗失败的可能性。目前尚不清楚对三氯生敏感性降低的分离株在现实世界条件下会在多大程度上发展并具有生存适应性。
