Medical Microbiology and Molecular Biology Laboratory, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, UP, India.
Lett Appl Microbiol. 2013 Oct;57(4):325-9. doi: 10.1111/lam.12116. Epub 2013 Jul 3.
Recently, it was speculated that human serum albumin (HSA) possesses β-lactamase activity and could contribute to nonmicrobial-based antibiotic resistance, owing to its ability to hydrolyse the β-lactam ring of nitrocefin. Moreover, the putative β-lactamase activity of HSA has been shown to increase significantly in the presence of environmental pollutants (1-naphthol and 2-naphthol). It was postulated that HSA could also cleave the β-lactam ring of clinically significant antibiotics. We studied the β-lactamase activity of HSA on clinically significant antibiotics of cephalosporin group in the presence of environmental pollutants by determining specific activity, enzyme kinetics and minimum inhibitory concentrations (MIC). The specific activity of HSA on various cephalosporins was found to be 1181-34 550 times lower than that observed for recombinant CTX-M-15 (used as positive control). The catalytic efficiency (kcat /Km ) of HSA on nitrocefin hydrolysis was 126·7 times lower than that of recombinant CTX-M-15, and it has increased only 2- to 3-folds in the presence of environmental pollutants. Moreover, cephalosporins were not hydrolysed by HSA under experimental conditions. The MIC data also showed that HSA is incapable of hydrolysing cephalosporins. The study concludes that HSA is inefficient to cleave antibiotics of cephalosporin group and hence does not contribute to nonmicrobial-based antibiotic resistance.
Earlier reports showed that human serum albumin (HSA) possesses β-lactamase activity, owing to its ability to cleave nitrocefin, and thus contributes to antibiotic resistance. Also, its β-lactamase activity is augmented when exposed to pollutants. As nitrocefin is not an antibiotic of clinical use, the conclusion drawn does not represent a true scenario and is misleading. Our results showed that HSA is inefficient in cleaving nitrocefin as compared to a true β-lactamase (CTX-M-15) and is practically inactive on cephalosporin antibiotics even in the presence pollutants. The findings showed that HSA-mediated hydrolysis of β-lactam antibiotics does not contribute to antibiotic resistance.
最近有研究推测，人血清白蛋白（HSA）具有β-内酰胺酶活性，并且可能由于其能够水解硝嗪头孢菌素的β-内酰胺环而导致非微生物的抗生素耐药性。此外，HSA 的假定β-内酰胺酶活性在存在环境污染物（1-萘酚和 2-萘酚）时会显著增加。有人推测，HSA 还可以切割临床上重要的抗生素的β-内酰胺环。我们通过测定比活性、酶动力学和最低抑菌浓度（MIC），研究了环境污染物存在时 HSA 对头孢菌素类抗生素的β-内酰胺酶活性。发现 HSA 对各种头孢菌素的比活性比用作阳性对照的重组 CTX-M-15 低 1181-34550 倍。HSA 对硝嗪头孢菌素水解的催化效率（kcat/Km）比重组 CTX-M-15 低 126.7 倍，并且在存在环境污染物时仅增加了 2-3 倍。此外，在实验条件下 HSA 不能水解头孢菌素。MIC 数据也表明 HSA 不能水解头孢菌素。该研究得出的结论是，HSA 不能有效地切割头孢菌素类抗生素，因此不会导致非微生物的抗生素耐药性。
早期的报道表明，人血清白蛋白（HSA）具有β-内酰胺酶活性，这归因于其能够切割硝嗪头孢菌素，从而导致抗生素耐药性。此外，当暴露于污染物时，其β-内酰胺酶活性会增加。由于硝嗪头孢菌素不是临床上使用的抗生素，因此得出的结论并不代表真实情况，具有误导性。我们的结果表明，与真正的β-内酰胺酶（CTX-M-15）相比，HSA 切割硝嗪头孢菌素的效率较低，即使在存在污染物的情况下，HSA 对头孢菌素类抗生素的实际活性也较低。研究结果表明，HSA 介导的β-内酰胺抗生素水解不会导致抗生素耐药性。
