Mechanism and antibacterial synergies of poly(Dabco-BBAC) nanoparticles against multi-drug resistant Pseudomonas aeruginosa isolates from human burns

Pseudomonas (P). aeruginosa is a Gram-negative opportunistic bacterium, able to adapt to difficult conditions and cause infectious diseases, such as cystic fibrosis, chronic wound and nosocomial infections. Some infections can have high mortality due to its inherent and acquired resistance to broad-spectrum antibiotics [1], [2].

Among all hospital patients, burn victims are highly susceptible to infection with pathogens, especially P. aeruginosa from both the environment and their skin. Furthermore, due to the coronavirus disease 2019 (COVID-19) pandemic and the serious damage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produces in the immune system, hospitalized patients are in even more danger of acquiring multi drug resistant (MDR) healthcare-associated infections (HAI) from other patients, personnel, and surfaces [3], [4]. Although there are diverse generic antibiotics used to combat bacteria, antibiotic-resistant bacteria create huge problems in medical care and hospital procedures [5].

In this regard, there is an urgent need for alternative antibacterial agents to battle MDR species. In recent decades, nanotechnology has produced several innovative antibacterial compositions, with a critical role in overcoming MDR bacteria, especially P. aeruginosa, and could be an alternative to traditional antibiotics [6], [7].

There have been a large number of studies so far describing antibacterial nanoparticles (NPs) and nanocomposites. Many of these have used metal nanoparticles, such as gold nanoparticles (AuNPs) or silver nanopatrticles (AgNPs). For example, in 2021 a chitosan-based AuNP composition was described by Mu et al. and showed good antibacterial effects in burn-wound infection [8]. Moreover, Nozari and coworkers designed novel zinc oxide nanoparticles for accelerating healing of skin burn wounds [9]. Additionally, several articles have reported the antibacterial activity of AgNPs against MDR bacteria and P. aeruginosa [10]. Nevertheless, some metal nanoparticles may have disadvantages, such as cytotoxicity, uncontrollable agglomeration, etc. [11], [12]. To overcome these problems numerous solutions have been proposed. One example is the use of cationic nano-polymers as antibacterial agents, which not only show low toxicity, but also have good antibacterial activity due to their ability to interact with the negative charge of the bacterial cell membrane [13], [14].

In this respect, in 2022 our group designed a novel cationic nanopolymer called poly(DABCO-BBAC) NPs which showed good antibacterial effects against four ATCC species including P. aeruginosa, Escherichia. coli, Enterococcus faecalis and staphylococcus aureus [15]. Here, for the first time, we evaluate the antibacterial activity of poly(DABCO-BBAC) against eight multi-drug resistant P. aeruginosa isolates from human burn infections, in planktonic and biofilm cells. We test the possible synergistic effects of poly(DABCO-BBAC) in combination with gentamicin, and investigate the mechanism of antibacterial activity of poly(DABCO-BBAC) by molecular and microscopic methods.

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