The Background Behind The Alpelisib Accomplishments
Both strains had evidence of biofilms, identified as dense microcolonies using microscopic techniques. The passaged MRSA resulted in more frequent bacterial colonies, which occurred in a concatenated structure. Zhao et al.29 further confirmed the presence of biofilms and their effect on wound healing using infection with a P. aeruginosa PA01 strain in a db/db mouse model. Pseudomonas biofilms were transferred onto a 2 day old wound that was created on the dorsal surface of mice, and none of the biofilm-infected wounds healed after 4 weeks. However, after 6 weeks 64% of the biofilm-infected wounds healed and all biofilm-infected wounds healed by 8 weeks. Although biofilms delayed wound healing, the wounds did eventually heal. Watters et al.,30 using an in vivo diabetic mouse chronic wound model, investigated the effect of a P. aeruginosa biofilm on healing. As noted by others, P. aeruginosa biofilm impaired healing. Of note, they found that the prevalence density of the P. aeruginosa biofilm increased when the mice were treated with insulin, suggesting that the diabetic wound environment may promote the formation of a biofilm. Nguyen et al.31 evaluated host responses in biofilm-infected wounds using the TallyHo mouse model of type 2 diabetes. They noted that these diabetic biofilm-containing wounds had significantly less TLP 2, TLR 4, interleukin-1 beta, and tumor PI3K inhibitor necrosis factor-alpha than wild type wounds with biofilm and less neutrophil oxidative burst activity. Thompson et al.32 reported on an excisional murine wound model to investigate the effect of a multidrug resistant Acinetobacter baumannii. A 6?mm diameter full-thickness wound was created and inoculated with A. baumannii. Amongst bioburden and other tests, the wound was assessed for biofilms using SEM and PNA-FISH. In a study designed to explore the role of QS and P. aeruginosa biofilm in a pressure ulcer model in rats, Nakagami et al.33 found that day 3 postwounding, the biofilm formation was immature in QS-deficient strains, with a lack of dense bacterial aggregates and EPS. The immature biofilm did, however, induce inflammation in the early development phase. Asada et al.,34 using P. aeruginosa to study wound colonization (biofilms) and wound infections in 6 month old rats, also concluded that biofilms delayed wound healing. Trostrup et al.35 developed a chronic P. aeruginosa biofilm infection model in C3H/HeN and BALB/c mice. They induced third-degree thermal lesions with full-thickness skin necrosis and infected them with P. aeruginosa. PNA-FISH and DAPI staining revealed bacteria within a cluster formation, identified as biofilm. Furthermore, the P. aeruginosa biofilm induced local inflammation. Given the polymicrobial nature of nonhealing wounds, it is important to gain an understanding of the development of mixed species biofilms and the ways in which they affect wound healing. Seth et al.