Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites.
Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites.
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DOI：
10.1038/s41467-023-40872-z
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发表时间：
2023-08-22
影响因子：
16.6
通讯作者：
McDonald, Julie A. K.
中科院分区：
文献类型：
--
作者：
Yip, Alexander Y. G.;King, Olivia G.;Omelchenko, Oleksii;Kurkimat, Sanjana;Horrocks, Victoria;Mostyn, Phoebe;Danckert, Nathan;Ghani, Rohma;Satta, Giovanni;Jauneikaite, Elita;Davies, Frances J.;Clarke, Thomas B.;Mullish, Benjamin H.;Marchesi, Julian R.;McDonald, Julie A. K.
肠道是碳青霉烯耐药肠杆菌科（CRE）的主要定植位点，并作为CRE的储存库，导致侵袭性感染（例如血液感染）。广谱抗生素破坏由肠道微生物群介导的定植抗性，促进肠道内CRE的扩张。在这里，我们表明抗生素诱导的肠道微生物种群减少导致营养物质的富集和抑制性代谢物的消耗，从而促进CRE的生长。抗生素降低了人类粪便微生物群离体培养中肠道共生菌（包括双歧杆菌科和拟杆菌科）的丰度；这伴随着微生物代谢物的消耗和营养物质的富集。我们测量了几种CRE菌株的营养利用能力、营养偏好和代谢物抑制敏感性。我们发现CRE可以利用抗生素处理后富集的营养物质作为生长的碳氮源。这些营养物质在抗生素治疗小鼠的粪便中也会增加，并在碳青霉烯抗性大肠杆菌肠道定植后减少。此外，某些微生物代谢物（在抗生素治疗后耗尽）抑制CRE的生长。我们的研究结果表明，用抗生素杀死肠道共生菌通过丰富营养和消耗抑制性微生物代谢物促进CRE定植。广谱抗生素可以杀死肠道内无害的细菌，从而促进耐抗生素细菌的入侵，如碳青霉烯耐药肠杆菌科（CRE）。在这里，Yip等人表明，用抗生素杀死肠道细菌会导致营养物质的富集和抑制性微生物代谢物的消耗，这总体上增强了CRE的生长。
The intestine is the primary colonisation site for carbapenem-resistant Enterobacteriaceae (CRE) and serves as a reservoir of CRE that cause invasive infections (e.g. bloodstream infections). Broad-spectrum antibiotics disrupt colonisation resistance mediated by the gut microbiota, promoting the expansion of CRE within the intestine. Here, we show that antibiotic-induced reduction of gut microbial populations leads to an enrichment of nutrients and depletion of inhibitory metabolites, which enhances CRE growth. Antibiotics decrease the abundance of gut commensals (including Bifidobacteriaceae and Bacteroidales) in ex vivo cultures of human faecal microbiota; this is accompanied by depletion of microbial metabolites and enrichment of nutrients. We measure the nutrient utilisation abilities, nutrient preferences, and metabolite inhibition susceptibilities of several CRE strains. We find that CRE can use the nutrients (enriched after antibiotic treatment) as carbon and nitrogen sources for growth. These nutrients also increase in faeces from antibiotic-treated mice and decrease following intestinal colonisation with carbapenem-resistant Escherichia coli. Furthermore, certain microbial metabolites (depleted upon antibiotic treatment) inhibit CRE growth. Our results show that killing gut commensals with antibiotics facilitates CRE colonisation by enriching nutrients and depleting inhibitory microbial metabolites. Broad-spectrum antibiotics can kill harmless bacteria in our intestine, thus facilitating invasion by antibiotic-resistant bacteria such as carbapenem-resistant Enterobacteriaceae (CRE). Here, Yip et al. show that killing gut bacteria with antibiotics leads to enrichment of nutrients and depletion of inhibitory microbial metabolites, which overall potentiates CRE growth.
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影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
DOI：
10.1093/jac/dkaa345
发表时间：
2020-12-01
期刊：
The Journal of antimicrobial chemotherapy
影响因子：
--
作者：
Bortolaia V;Kaas RS;Ruppe E;Roberts MC;Schwarz S;Cattoir V;Philippon A;Allesoe RL;Rebelo AR;Florensa AF;Fagelhauer L;Chakraborty T;Neumann B;Werner G;Bender JK;Stingl K;Nguyen M;Coppens J;Xavier BB;Malhotra-Kumar S;Westh H;Pinholt M;Anjum MF;Duggett NA;Kempf I;Nykäsenoja S;Olkkola S;Wieczorek K;Amaro A;Clemente L;Mossong J;Losch S;Ragimbeau C;Lund O;Aarestrup FM
通讯作者：
Aarestrup FM
影响因子：
1.7
作者：
Bankevich, Anton;Nurk, Sergey;Pevzner, Pavel A.
通讯作者：
Pevzner, Pavel A.
DOI：
10.1016/j.jcmgh.2021.02.007
发表时间：
2021
影响因子：
7.2
作者：
Ghosh S;Whitley CS;Haribabu B;Jala VR
通讯作者：
Jala VR
影响因子：
4.2
作者：
Engevik MA;Danhof HA;Hall A;Engevik KA;Horvath TD;Haidacher SJ;Hoch KM;Endres BT;Bajaj M;Garey KW;Britton RA;Spinler JK;Haag AM;Versalovic J
通讯作者：
Versalovic J