Motiwala Tehrim, Nyide Babalwa, Khoza Thandeka
Department of Biochemistry, School of Life Sciences, Pietermaritzburg Campus, University of KwaZulu-Natal, Pietermaritzburg, South Africa.
Front Bioinform. 2025 Mar 25;5:1498916. doi: 10.3389/fbinf.2025.1498916. eCollection 2025.
The complex (ECC) consists of six species (, , , , and ) that have emerged as nosocomial pathogens of interest, with and being the most frequently isolated ECC species in human clinical specimens and intensive care unit (ICU) patients. Many nosocomial outbreaks of have been related to transmission through contaminated surgical equipment and operative cleaning solutions. As this pathogen evades the action of antibiotics, it is important to find alternative targets to limit the devastating effects of these pathogens. ClpV is a Clp ATPase which dissociates and recycles the contracted sheath of the bacterial type VI secretion system (T6SS), thereby regulating bacterial populations and facilitating environmental colonization. Seventy-one strains were mined for Clp ATPase proteins. All the investigated strains contained ClpA, ClpB, ClpX and ClpV while only 20% contained ClpK. All the investigated strains contained more than one ClpV protein, and the ClpV proteins showed significant variations. Three ClpV proteins from strain E3442 were then investigated to determine the structural difference between each protein. Homology modelling showed the proteins to be structurally similar to each other, however the physicochemical characteristics of the proteins vary. Additionally, physicochemical analysis and molecular dynamic simulations showed that the proteins were highly dynamic and not significantly different from each other. Further investigation of the proteins and in the presence and absence of various ligands and proteins could be performed to determine whether the proteins all interact with their surroundings in the same manner. This would allow one to determine why multiple homologs of the same protein are expressed by pathogens.
该复合体（ECC）由六种菌株（、、、、和）组成，这些菌株已成为备受关注的医院病原体，其中和是人类临床标本和重症监护病房（ICU）患者中最常分离出的ECC菌株。许多医院内的爆发都与通过受污染的手术设备和手术清洁溶液传播有关。由于这种病原体能逃避抗生素的作用，因此找到替代靶点以限制这些病原体的破坏性影响非常重要。ClpV是一种Clp ATP酶，它能使细菌VI型分泌系统（T6SS）收缩的鞘解离并循环利用，从而调节细菌数量并促进在环境中的定殖。对71株菌株的Clp ATP酶蛋白进行了挖掘。所有研究的菌株都含有ClpA、ClpB、ClpX和ClpV，而只有20%含有ClpK。所有研究的菌株都含有不止一种ClpV蛋白，并且ClpV蛋白表现出显著差异。然后对菌株E3442的三种ClpV蛋白进行了研究，以确定每种蛋白之间的结构差异。同源建模显示这些蛋白在结构上彼此相似，然而这些蛋白的物理化学特性有所不同。此外，物理化学分析和分子动力学模拟表明这些蛋白具有高度动态性且彼此之间没有显著差异。可以在有和没有各种配体及蛋白的情况下对蛋白和进行进一步研究，以确定这些蛋白是否都以相同方式与周围环境相互作用。这将有助于确定病原体为何会表达同一蛋白的多个同源物。
