Antimicrobial activity of carbon monoxide-releasing molecule [Mn(CO)3(tpa-κ3N)]Br versus multidrug-resistant isolates of Avian Pathogenic Escherichia coli and its synergy with colistin.
Antimicrobial activity of carbon monoxide-releasing molecule [Mn(CO)3(tpa-κ3N)]Br versus multidrug-resistant isolates of Avian Pathogenic Escherichia coli and its synergy with colistin.
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DOI：
10.1371/journal.pone.0186359
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
La Ragione RM
中科院分区：
文献类型：
--
作者：
Betts J;Nagel C;Schatzschneider U;Poole R;La Ragione RM
抗生素耐药性是人类和兽医学中日益增长的全球性问题，临床医生的武器库中的空白不断增加。新型化合物，包括一氧化碳释放分子（CORM），例如光活化金属络合物[Mn（CO）3（tpa-κ 3 N）]Br，可以用作替代品/补充传统的抗菌药物。禽源致病性大肠杆菌（Avian pathogenic Escherichia coli，APEC）与人类致病性大肠杆菌（human pathogenic Escherichia coli，human pathogenic Escherichia coli，human pathogenic E.杆菌通过肉汤微量滴定稀释试验和使用棋盘和时间杀灭试验进行的与粘菌素的协同作用试验，评估[Mn（CO）3（tpa-κ 3 N）]Br对多药耐药APEC的体外活性。使用大蜡螟幼虫模型测定[Mn（CO）3（tpa-κ 3 N）]Br单独和与粘菌素组合的体内抗菌活性。监测动物的存活/死亡、黑化和从幼虫血淋巴中计数的细菌数量。体外试验产生相对较高的[Mn（CO）3（tpa-κ 3 N）]Br最低抑制浓度（MIC）为1024 mg/L。然而，随着粘菌素的加入，其活性显著增加，使MIC降至≤32 mg/L。这种协同作用在时间杀灭测定中得到证实。体内试验表明，[Mn（CO）3（tpa-κ 3 N）]Br与粘菌素的组合产生了上级的细菌杀灭作用，并显著提高了幼虫存活率。在体外和体内试验中，抗菌活性不需要光激活。该数据支持进一步评价[Mn（CO）3（tpa-κ 3 N）]Br作为治疗人类和动物全身性感染的潜在药物，当与透化剂如粘菌素一起使用时。
Antimicrobial resistance is a growing global concern in human and veterinary medicine, with an ever-increasing void in the arsenal of clinicians. Novel classes of compounds including carbon monoxoide-releasing molecules (CORMs), for example the light-activated metal complex [Mn(CO)3(tpa-κ3N)]Br, could be used as alternatives/to supplement traditional antibacterials. Avian pathogenic Escherichia coli (APEC) represent a large reservoir of antibiotic resistance and can cause serious clinical disease in poultry, with potential as zoonotic pathogens, due to shared serotypes and virulence factors with human pathogenic E. coli. The in vitro activity of [Mn(CO)3(tpa-κ3N)]Br against multidrug-resistant APECs was assessed via broth microtitre dilution assays and synergy testing with colistin performed using checkerboard and time-kill assays. In vivo antibacterial activity of [Mn(CO)3(tpa-κ3N)]Br alone and in combination with colistin was determined using the Galleria mellonella wax moth larvae model. Animals were monitored for life/death, melanisation and bacterial numbers enumerated from larval haemolymph. In vitro testing produced relatively high [Mn(CO)3(tpa-κ3N)]Br minimum inhibitory concentrations (MICs) of 1024 mg/L. However, its activity was significantly increased with the addition of colistin, bringing MICs down to ≤32 mg/L. This synergy was confirmed in time-kill assays. In vivo assays showed that the combination of [Mn(CO)3(tpa-κ3N)]Br with colistin produced superior bacterial killing and significantly increased larval survival. In both in vitro and in vivo assays light activation was not required for antibacterial activity. This data supports further evaluation of [Mn(CO)3(tpa-κ3N)]Br as a potential agent for treatment of systemic infections in humans and animals, when used with permeabilising agents such as colistin.
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DOI：
10.3390/ijerph7010089
发表时间：
2010-01
影响因子：
--
作者：
Lutful Kabir SM
通讯作者：
Lutful Kabir SM
影响因子：
1.4
作者：
La Ragione, R. M.;Woodward, M. J.;Karaca, K.
通讯作者：
Karaca, K.
影响因子：
--
作者：
Ward, Jonathan S.;Morgan, Rebecca;Moir, James W. B.
通讯作者：
Moir, James W. B.
影响因子：
56.3
作者：
Liu, Yi-Yun;Wang, Yang;Shen, Jianzhong
通讯作者：
Shen, Jianzhong
用于研究细菌疾病和抗菌药物测试的梅洛尼菌感染模型。
影响因子：
5.2
作者：
Tsai CJ;Loh JM;Proft T
通讯作者：
Proft T