Vander Elst Niels, Linden Sara B, Lavigne Rob, Meyer Evelyne, Briers Yves, Nelson Daniel C
Laboratory of Biochemistry, Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium.
Laboratory of Antimicrobial Discovery, Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA.
Antibiotics (Basel). 2020 Sep 19;9(9):621. doi: 10.3390/antibiotics9090621.
Bovine mastitis, an infection of the cow's mammary gland, is frequently caused by and causes major economic losses in the dairy industry. The intramammary administration of antibiotics currently remains the predominant preventive and therapeutic measure. These antimicrobial compounds, of which some are considered critical in human health care, are frequently applied as dry therapy resulting in their consistent overuse. Therefore, the use of antibiotics in the dairy sector is being questioned. We here identified two endolysins, i.e., PlySs2 and PlySs9, respectively derived from serotype-2 and -9 prophages, with lytic activity against in an in vitro setting. Both endolysins gave clear lysis zones in spot-on-plate assays and caused a reduction of the optical density in a turbidity reduction assay. In depth characterization identified PlySs9 as the more potent endolysin over PlySs2 with a lower MIC value and about one additional log of killing. PlySs2 and PlySs9 were challenged to a panel of subclinical and clinical milk isolates and were both able to lyse all strains tested. Molecular dissection of these endolysins in catalytic and cell wall binding subdomains resulted in major loss of killing and binding activity, respectively. Taken together, we here propose PlySs2 and PlySs9 as candidate compounds to the current antimicrobial arsenal known against bovine mastitis-causing as future add-on or replacement strategy to the currently used intramammary antibiotics.
牛乳腺炎是奶牛乳腺的一种感染疾病，常由[具体病因未提及]引起，给乳制品行业造成重大经济损失。目前，乳房内注射抗生素仍然是主要的预防和治疗措施。这些抗菌化合物中有些在人类医疗保健中被视为关键药物，常作为干奶期治疗药物使用，导致其持续过度使用。因此，乳制品行业中抗生素的使用受到质疑。我们在此鉴定出两种内溶素，即分别源自血清型2和9的前噬菌体的PlySs2和PlySs9，它们在体外对[具体细菌未提及]具有裂解活性。在点滴平板试验中，这两种内溶素均产生了清晰的裂解圈，并且在比浊法试验中导致光密度降低。深入表征表明，PlySs9是比PlySs2更有效的内溶素，其最低抑菌浓度（MIC）值更低，杀菌能力约高出一个对数级。用一组亚临床和临床[具体细菌未提及]牛奶分离株对PlySs2和PlySs9进行测试，它们均能裂解所有测试菌株。对这些内溶素的催化和细胞壁结合亚结构域进行分子剖析，分别导致杀菌活性和结合活性大幅丧失。综上所述，我们在此提议将PlySs2和PlySs9作为对抗引起牛乳腺炎的[具体细菌未提及]的现有抗菌药物库的候选化合物，作为当前乳房内使用抗生素的未来附加或替代策略。
