Daptomycin (DAP) is one of the most potent antibiotics used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Due to an increase in its administration for combating MRSA infections, DAP non-susceptible (DAP-NS) MRSA strains have recently been reported in clinical settings. The presence of single nucleotide polymorphisms (SNPs) in the multiple peptide resistance factor (mprF) gene is the most frequently reported cause for the evolution of DAP-NS MRSA strains; however, there are some variations of SNPs that could lead to DAP-NS. In this study, we used two clinical MRSA strains, including DAP susceptible (DAP-S) and DAP-NS, isolated from the same patient at different time points. We introduced T345I SNP to mprF of the DAP-S MRSA strain using the gene exchange method with pIMAY vector. Further, we investigated the phenotype of the mutant strain, including drug susceptibility, cell surface positive charge, and growth speed. The mutant strain exhibited (i) resistance to DAP, (ii) up-regulation of positive surface charge, (iii) slower growth speed, and (iv) thickened cell walls. Hence, the SNP in mprF may have caused an up-regulation in MprF function, with a subsequent increase in positive surface charge. Cumulatively, these results demonstrated that the T345I amino acid substitution in mprF represents one of the primary causes of DAP-NS in MRSA strains.

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Blood-feeding arthropods, particularly ticks and mosquitoes are considered the most important vectors of arthropod-borne diseases affecting humans and animals. While feeding on blood meals, arthropods are exposed to high levels of reactive oxygen species (ROS) since heme and other blood components can induce oxidative stress. Different ROS have important roles in interactions among the pathogens, vectors, and hosts. ROS influence various metabolic processes of the arthropods and some have detrimental effects. In this review, we investigate the various roles of ROS in these arthropods, including their innate immunity and the homeostasis of their microbiomes, that is, how ROS are utilized to maintain the balance between the natural microbiota and potential pathogens. We elucidate the mechanism of how ROS are utilized to fight off invading pathogens and how the arthropod-borne pathogens use the arthropods’ antioxidant mechanism to defend against these ROS attacks and their possible impact on their vector potentials or their ability to acquire and transmit pathogens. In addition, we describe the possible roles of ROS in chemical insecticide/acaricide activity and/or in the development of resistance. Overall, this underscores the importance of the antioxidant system as a potential target for the control of arthropod and arthropod-borne pathogens.

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