Emergence of phylogenetically diverse and fluoroquinolone resistant Salmonella Enteritidis as a cause of invasive nontyphoidal Salmonella disease in Ghana
Emergence of phylogenetically diverse and fluoroquinolone resistant Salmonella Enteritidis as a cause of invasive nontyphoidal Salmonella disease in Ghana
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DOI：
10.1371/journal.pntd.0007485
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发表时间：
2019-06-01
影响因子：
3.8
通讯作者：
Eibach, Daniel
中科院分区：
文献类型：
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作者：
Aldrich, Cassandra;Hartman, Hassan;Eibach, Daniel
肠炎沙门氏菌是全球家禽和鸡蛋相关性小肠结肠炎和撒哈拉以南非洲地区血液侵袭性非伤寒沙门氏菌(INTS)疾病的一种病因。最近描述了与SSA的INTS病相关的独特的、多药耐药的基因型别，通常需要用氟喹诺酮类抗生素治疗。在工业化国家，在家禽生产中使用抗菌剂已导致全球流行的小肠结肠炎相关品系对氟喹诺酮类药物产生频繁耐药性。方法/主要结果2007年至2015年在加纳阿散蒂地区收集的27株肠炎葡萄球菌和2株家禽分离株进行了全基因组测序。这些以环丙沙星敏感率(DC)降低而闻名的菌株被置于英国公共卫生(PHE)肠炎链球菌基因组数据库中1,067个序列的系统学背景中，以了解DC是否与肠炎链球菌非洲分支或全球流行分支有关。分析显示，肠炎沙门氏菌的四个主要分支有代表，两个全球分支和两个非洲分支。所有13株鸭瘟病毒分离株在第87位密码子上含有单一gyrA突变，属于与家禽相关的小肠结肠炎流行的全球PT4类分支。除了两个与前往西班牙和巴西的Phe分离株聚在一起的DCS群外，其余的DCS群，包括一个家禽分离株，属于两个单系群，其中GyrA 87似乎在该地区发生了突变。结论/意义在加纳与INTS疾病相关的肠炎链霉菌之间存在着明显的系统发育多样性。耐药谱因分支不同而不同，突显了制定实验性脓毒症指南的挑战。在与种系相关的家禽和人类分离株中检测到氟喹诺酮耐药性是主要关注的问题，该地区蓬勃发展的家禽业需要采取监测和控制措施来保护INTS疾病的高风险人群。肠炎沙门氏菌既是人畜共患胃肠炎的主要全球原因，与鸡蛋和家禽的工业化生产有关，也是撒哈拉以南非洲地区血液侵袭性感染的主要原因，这种临床综合征被称为侵袭性非伤寒沙门氏菌(INTS)病。非洲流行的INTS菌株往往具有多重耐药性，使得氟喹诺酮类抗生素成为降低INTS相关发病率和死亡率的关键因素。我们分析了从加纳收集的肠炎沙门氏菌的基因组，以调查该地区出现氟喹诺酮耐药的情况。目前存在广泛的系统发育多样性，然而，氟喹诺酮耐药仅限于一个分支，导致家禽相关性胃肠炎的全球流行。这种阻力主要是在当地出现的，而不是从国外传入的。我们发现，肠炎链球菌的耐药性模式不同，这突显了在缺乏诊断微生物学设施来监测耐药性变化的情况下，设计经验脓毒症治疗指南的挑战。此外，我们在密切相关的家禽和人类分离株中检测到氟喹诺酮类耐药性，这表明在不断增长的本地家禽行业中，抗菌剂的使用在推动耐药性的出现方面发挥了作用，该行业内需要采取监测措施，以保护INTS疾病的高风险人群。
Background Salmonella enterica serovar Enteritidis is a cause of both poultry- and egg-associated enterocolitis globally and bloodstream-invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa (sSA). Distinct, multi-drug resistant genotypes associated with iNTS disease in sSA have recently been described, often requiring treatment with fluoroquinolone antibiotics. In industrialised countries, antimicrobial use in poultry production has led to frequent fluoroquinolone resistance amongst globally prevalent enterocolitis-associated lineages.Methodology/Principal findings Twenty seven S. Enteritidis isolates from patients with iNTS disease and two poultry isolates, collected between 2007 and 2015 in the Ashanti region of Ghana, were whole-genome sequenced. These isolates, notable for a high rate of diminished ciprofloxacin susceptibility (DCS), were placed in the phyletic context of 1,067 sequences from the Public Health England (PHE) S. Enteritidis genome database to understand whether DCS was associated with African or globally-circulating clades of S. Enteritidis. Analysis showed four of the major S. Enteritidis clades were represented, two global and two African. All thirteen DCS isolates, containing a single gyrA mutation at codon 87, belonged to a global PT4-like clade responsible for epidemics of poultry-associated enterocolitis. Apart from two DCS isolates, which clustered with PHE isolates associated with travel to Spain and Brazil, the remaining DCS isolates, including one poultry isolate, belonged to two monophyletic clusters in which gyrA 87 mutations appear to have developed within the region.Conclusions/Significance Extensive phylogenetic diversity is evident amongst iNTS disease-associated S. Enteritidis in Ghana. Antimicrobial resistance profiles differed by clade, highlighting the challenges of devising empirical sepsis guidelines. The detection of fluoroquinolone resistance in phyletically-related poultry and human isolates is of major concern and surveillance and control measures within the region's burgeoning poultry industry are required to protect a human population at high risk of iNTS disease.Author summary Salmonella enterica serovar Enteritidis is both a prominent global cause of zoonotic gastroenteritis, in association with the industrial production of eggs and poultry, and of bloodstream-invasive infection in sub-Saharan Africa, a clinical syndrome referred to as invasive nontyphoidal Salmonella (iNTS) disease. African epidemic iNTS strains are frequently multi-drug resistant, leaving fluoroquinolone antibiotics as key agents in reducing iNTS-associated morbidity and mortality. We analysed the genomes of S. Enteritidis collected in Ghana from patients with iNTS disease to investigate the emergence of fluoroquinolone resistance in the region. Extensive phylogenetic diversity was present, however, fluoroquinolone resistance was confined to a single clade causing global epidemics of poultry-associated gastroenteritis. This resistance has predominantly emerged locally, rather than being imported. We found that antimicrobial resistance patterns differed by S. Enteritidis clade, highlighting the challenges of devising empirical sepsis treatment guidelines in the absence of diagnostic microbiology facilities to monitor changes in resistance profiles. Furthermore, we detected fluoroquinolone resistance in closely related poultry and human isolates, suggesting a role of antimicrobial use within the growing local poultry industry in driving the emergence of resistance and a need for surveillance measures within this industry to protect a human population at high risk of iNTS disease.