Stercz Balazs, Domokos Judit, Dunai Zsuzsanna A, Makra Nora, Juhasz Janos, Ostorhazi Eszter, Kocsis Bela, Szabo Dora
Institute of Medical Microbiology, Semmelweis University, 1089 Budapest, Hungary.
HUN-REN-SU Human Microbiota Research Group, 1052 Budapest, Hungary.
Antibiotics (Basel). 2024 Jul 26;13(8):698. doi: 10.3390/antibiotics13080698.
The asymptomatic gastrointestinal colonization of multidrug-resistant (MDR) bacteria can lead to difficult-to-treat infections. We investigated the role of host factors influencing colonization in an orogastrical murine infection model using a CTX-M-15- and OXA-162-producing ST15 (MDR-KP) strain, as well as J53 (EC) and transconjugants with an IncFII(K) plasmid carrying CTX-M-15 (EC-CTXM), and with an IncL plasmid carrying OXA-162 (EC-OXA) genes. The fecal bacterial count in colony-forming unit/gram stool (CFU/g) was determined by cultivation, IgA and defensin levels by ELISA, and gut microbiota by 16S rRNA analysis. The CFU was the lowest in EC, followed by EC-OXA and EC-CTXM, and the highest in the MDR-KP group. The IgA level in feces increased in MDR-KP, EC-CTXM, and EC-OXA, and did not change in EC. The beta-defensin 3 level markedly increased in all groups, with the highest values in MDR-KP and EC-CTXM. Alpha-defensin-5 increased in all groups especially in EC. In microbiota, the phylum was dominant in MDR-KP, EC-CTXM, and EC-OXA, whereas was dominant in EC. The family was significantly more common in the MDR-KP and EC-OXA groups, while the family was dominant in the EC group. While fecal IgA levels positively correlated with colonizing bacterial CFU, the alpha-defensin 5 levels inversely correlated with CFUs and IgA levels. The presence of the IncFII(K) plasmid induced beta-defensin 3 production. The amounts of the family members exhibited a correlation with the IncL plasmid. The detected amounts of the family indicated the protective role against the high-risk clone and the resistance plasmids' dissemination. Our results suggest that not only the MDR-KP clone itself but also the resistance plasmids play a primary role in the colonization rate in the gastrointestinal tract. Both the MDR-KP clone as well as the IncFII(K) and IncL resistance plasmids provide survival and colonization benefits in the gut.
多重耐药（MDR）菌的无症状胃肠道定植可导致难以治疗的感染。我们在一个经口胃的小鼠感染模型中，使用一株产CTX-M-15和OXA-162的ST15（MDR-KP）菌株，以及J53（EC）和携带携带CTX-M-15的IncFII(K)质粒的接合子（EC-CTXM）和携带携带OXA-162基因的IncL质粒的接合子（EC-OXA），研究了影响定植的宿主因素的作用。通过培养测定每克粪便中菌落形成单位（CFU/g）的粪便细菌计数，通过酶联免疫吸附测定法（ELISA）测定IgA和防御素水平，并通过16S rRNA分析测定肠道微生物群。CFU在EC中最低，其次是EC-OXA和EC-CTXM，在MDR-KP组中最高。粪便中的IgA水平在MDR-KP、EC-CTXM和EC-OXA中升高，而在EC中未变化。β-防御素3水平在所有组中均显著升高，在MDR-KP和EC-CTXM中最高。α-防御素-5在所有组中均升高，尤其是在EC中。在微生物群中，MDR-KP、EC-CTXM和EC-OXA中 门占优势，而EC中 门占优势。 科在MDR-KP和EC-OXA组中显著更常见，而 科在EC组中占优势。虽然粪便IgA水平与定植细菌CFU呈正相关，但α-防御素5水平与CFU和IgA水平呈负相关。IncFII(K)质粒的存在诱导β-防御素3的产生。 科成员的数量与IncL质粒呈相关性。检测到的 科数量表明其对高风险克隆和耐药质粒传播具有保护作用。我们的结果表明，不仅MDR-KP克隆本身，而且耐药质粒在胃肠道定植率中起主要作用。MDR-KP克隆以及IncFII(K)和IncL耐药质粒都为在肠道中的存活和定植提供了益处。
