Comparative genomics reveals the correlations of stress response genes and bacteriophages in developing antibiotic resistance of Staphylococcus saprophyticus.
Comparative genomics reveals the correlations of stress response genes and bacteriophages in developing antibiotic resistance of Staphylococcus saprophyticus.
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DOI：
10.1128/msystems.00697-23
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发表时间：
2023-12-21
期刊：
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
--
作者：
金黄色葡萄球菌是导致非复杂性尿路感染的主要革兰氏阳性菌。最近的报道增加抗菌药物耐药性（AMR）在S。sachticus值得研究其未充分研究的耐药模式。在这里，我们描述了一个不同的收集S。sacchariticus（n = 275）进行比较全基因组测序。我们对核心基因（1,646个）进行了系统发育分析，将我们的S。并研究了抗生素抗性基因（ARG）的分布。S. 275株沙门氏菌中有14.91%（41/275）表现为多重耐药。我们比较了我们的S。具有不同的ARG和基因等位基因的存在。29.8%（82/275）携带葡萄球菌盒式染色体移动的元件，其中25.6%（21/82）为mecA+。青霉素耐药性与mecA或blaZ的存在相关。mecA基因可作为沙门氏菌对头孢西丁和苯唑西林耐药的标记。sacchariticus，但该基因的缺失并不能预测易感性。利用计算模型，我们发现几个基因与mecA−分离株中的头孢西丁和苯唑西林耐药性相关，其中一些基因在应激反应和细胞壁合成中具有预测功能。此外，表型关联分析表明，其他葡萄球菌中报告的针对非β-内酰胺类药物的ARG可能是S.萨皮提库斯最后，我们观察到噬菌体携带的两种ARG [ARG和ARG（44）v]与对红霉素（11/11和10/10）和克林霉素（11/11和10/10）的高表型不敏感性相关。本研究中鉴定的AMR相关遗传元件有助于完善抗虫性预测。抗生素治疗期间的溶血性链球菌金黄色葡萄球菌是与女性尿路感染（UTIs）相关的第二大常见细菌。无并发症的UTI的抗菌治疗方案通常是呋喃妥因、甲氧苄啶-磺胺甲恶唑（TMP-SMX）或氟喹诺酮类药物，无需进行常规的S.从尿液样本中发现的嗜酸链球菌。而抗TMP SMX的S.最近在UTI患者中以及在我们的队列中检测到了溶血性链球菌。在此，我们调查了未充分研究的耐药模式，这种致病性物种的基因组抗生素耐药基因（ARG）的内容，易感性表型。我们描述了ARG协会与已知的和新的SCCmec配置以及噬菌体元件在S。sacchariticus，可以作为干预或诊断目标，以限制耐药性传播。我们的分析产生了一个全面的数据库，表型数据相关的ARG序列在临床S。本研究为沙门氏菌的耐药性监测和预测提供了新的方法，为沙门氏菌的准确诊断和有效治疗奠定了基础。红蜘蛛UTIs.
Staphylococcus saprophyticus is the leading Gram-positive cause of uncomplicated urinary tract infections. Recent reports of increasing antimicrobial resistance (AMR) in S. saprophyticus warrant investigation of its understudied resistance patterns. Here, we characterized a diverse collection of S. saprophyticus (n = 275) using comparative whole genome sequencing. We performed a phylogenetic analysis of core genes (1,646) to group our S. saprophyticus and investigated the distributions of antibiotic resistance genes (ARGs). S. saprophyticus isolates belonged to two previously characterized lineages, and 14.91% (41/275) demonstrated multidrug resistance. We compared antimicrobial susceptibility phenotypes of our S. saprophyticus with the presence of different ARGs and gene alleles. 29.8% (82/275) carried staphylococcal cassette chromosome mobile elements, among which 25.6% (21/82) were mecA+. Penicillin resistance was associated with the presence of mecA or blaZ. The mecA gene could serve as a marker to infer cefoxitin and oxacillin resistance of S. saprophyticus, but the absence of this gene is not predictive of susceptibility. Utilizing computational modeling, we found several genes were associated with cefoxitin and oxacillin resistance in mecA− isolates, some of which have predicted functions in stress response and cell wall synthesis. Furthermore, phenotype association analysis indicates ARGs against non-β-lactams reported in other staphylococci may serve as resistance determinants of S. saprophyticus. Lastly, we observed that two ARGs [erm and erm (44)v], carried by bacteriophages, were correlated with high phenotypic non-susceptibility against erythromycin (11/11 and 10/10) and clindamycin (11/11 and 10/10). The AMR-correlated genetic elements identified in this work can help to refine resistance prediction of S. saprophyticus during antibiotic treatment. Staphylococcus saprophyticus is the second most common bacteria associated with urinary tract infections (UTIs) in women. The antimicrobial treatment regimen for uncomplicated UTI is normally nitrofurantoin, trimethoprim-sulfamethoxazole (TMP-SMX), or a fluoroquinolone without routine susceptibility testing of S. saprophyticus recovered from urine specimens. However, TMP-SMX-resistant S. saprophyticus has been detected recently in UTI patients, as well as in our cohort. Herein, we investigated the understudied resistance patterns of this pathogenic species by linking genomic antibiotic resistance gene (ARG) content to susceptibility phenotypes. We describe ARG associations with known and novel SCCmec configurations as well as phage elements in S. saprophyticus, which may serve as intervention or diagnostic targets to limit resistance transmission. Our analyses yielded a comprehensive database of phenotypic data associated with the ARG sequence in clinical S. saprophyticus isolates, which will be crucial for resistance surveillance and prediction to enable precise diagnosis and effective treatment of S. saprophyticus UTIs.
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影响因子：
16.6
作者：
Bradley P;Gordon NC;Walker TM;Dunn L;Heys S;Huang B;Earle S;Pankhurst LJ;Anson L;de Cesare M;Piazza P;Votintseva AA;Golubchik T;Wilson DJ;Wyllie DH;Diel R;Niemann S;Feuerriegel S;Kohl TA;Ismail N;Omar SV;Smith EG;Buck D;McVean G;Walker AS;Peto TE;Crook DW;Iqbal Z
通讯作者：
Iqbal Z
影响因子：
3.2
作者：
Donat, Stefanie;Streker, Karin;Ohlsen, Knut
通讯作者：
Ohlsen, Knut
影响因子：
15.5
作者：
Cook R;Hooton S;Trivedi U;King L;Dodd CER;Hobman JL;Stekel DJ;Jones MA;Millard AD
通讯作者：
Millard AD
影响因子：
3.4
作者：
de Sousa, Viviane Santos;de Souza da-Silva, Ana Paula;Moreira, Beatriz Meurer
通讯作者：
Moreira, Beatriz Meurer
影响因子：
3.9
作者：
Cortes, Marina F.;Botelho, Ana M. N.;Figueiredo, Agnes M. S.
通讯作者：
Figueiredo, Agnes M. S.