Evaluation of antimicrobial effects of photo-sonodynamic antimicrobial chemotherapy based on nano-micelle curcumin on virulence gene expression patterns in Acinetobacter baumannii

Background: Abaumannii baumannii rapidly resistance to a wide range of antimicrobial agents. The combination of antimicrobial photodynamic therapy (aPDT) and sonodynamic antimicrobial chemotherapy (SACT) known as photo-sonodynamic antimicrobial chemotherapy (PSACT) has received considerable attention as one of the emerging and promising strategies against microbial infections. Objective: This study aimed to investigate the antimicrobial effects of PSACT based on nano-micelle curcumin (N-MCur) on the virulence gene expression patterns in A. baumannii. Materials and methods: N-MCur as a photo-sonosensitizer was synthesized and confirmed. To determine sub-significant reduction dose of PSACT, sub-significant reduction dose of N-MCur and blue laser light during aPDT, and ultrasound power output during SACT were assessed. Finally, changes in the expression of genes involved in treated A. baumannii by minimum sub-significant reduction dose of PSACT were determined using quantitative real-time-PCR (qRT-PCR). Results: PSACT using 12.5 mM N-MCur at the ultrasound power outputs of 28.7, 36.9, and 45.2 mW/cm2 with 4 min irradiation time of blue laser, as well as, 6.2 mM N-MCur at an ultrasound power output of 45.2 mW/cm2 plus 3 min blue laser irradiation time exhibited the significant dose-dependent reduction against A. baumannii cell viability compared to the control group (P<0.05). After treatment of A. baumannii using 3.1 mM N-MCur + 2 min blue laser irradiation time + 28.7 mW/cm2 ultrasound as the minimum sub-significant reduction doses of PSACT, mRNA expression was significantly upregulated to 6.0-, 11.2-, and 13.7-folds in recA, blsA, and dnaK and downregulated to 8.6-, 10.1-, and 14.5-folds in csuE, espA, and abaI, respectively. Conclusions: N-MCur-mediated PSACT could regulate the expression of genes involved in A. baumannii pathogenesis. Therefore, PSACT can be proposed as a promising application to treat infections caused by A. baumannii.

Tissue compartmentalization enables Salmonella persistence during chemotherapy

Antimicrobial chemotherapy can fail to eradicate the pathogen, even in the absence of antimicrobial resistance. Persisting pathogens can subsequently cause relapsing diseases. In vitro studies suggest various mechanisms of antibiotic persistence, but their in vivo relevance remains unclear because of the difficulty of studying scarce pathogen survivors in complex host tissues. Here, we localized and characterized rare surviving Salmonella in mouse spleen using high-resolution whole-organ tomography. Chemotherapy cleared >99.5% of the Salmonella but was inefficient against a small Salmonella subset in the white pulp. Previous models could not explain these findings: drug exposure was adequate, Salmonella continued to replicate, and host stresses induced only limited Salmonella drug tolerance. Instead, antimicrobial clearance required support of Salmonella-killing neutrophils and monocytes, and the density of such cells was lower in the white pulp than in other spleen compartments containing higher Salmonella loads. Neutrophil densities declined further during treatment in response to receding Salmonella loads, resulting in insufficient support for Salmonella clearance from the white pulp and eradication failure. However, adjunctive therapies sustaining inflammatory support enabled effective clearance. These results identify uneven Salmonella tissue colonization and spatiotemporal inflammation dynamics as main causes of Salmonella persistence and establish a powerful approach to investigate scarce but impactful pathogen subsets in complex host environments.

Curcumin-mediated photodynamic antimicrobial chemotherapy (PACT): a systematic review / Quimioterapia fotodinâmica antimicrobiana (PACT) mediada por curcumina: uma revisão sistemática

Light energy is known to be used to combat microbial growth. Photodynamic antimicrobial chemotherapy (PACT) has the potential to use different naturally-occurring compounds, such as photosensitizers. Curcumin is an example of a molecule of interest in different areas under different optics. This systematic review surveys the aims and scope of research on curcumin-mediated PACT published between January 2011 and December 2020. The search was carried out in MEDLINE, PubMed, EMBASE and Periódicos CAPES databases employing the keywords “Photodynamic antimicrobial chemotherapy”, “photosensitizer”, “curcumin” and the descriptor “Light-Emitting Diode”. It was observed that in the last decade little material meeting these criteria was published. Brazilian institutions concentrated most of their studies on cytotoxic activity. The most recent work, however, focused on antibiofilm activity. Gram-positive bacteria are more sensitive to curcumin-mediated PACT over a short wavelength range. Different concentrations and exposure time of the photosensitizer were evaluated, but the amount of information is still insufficient to establish the best treatment condition as the number of tested pathogens is still poor.

Photodynamic antimicrobial chemotherapy coupled with the use of the photosensitizers methylene blue and temoporfin as a potential novel treatment for Staphylococcus aureus in burn infections

Photodynamic antimicrobial chemotherapy (PACT) is a novel alternative antimicrobial therapy that elicits a broad mechanism of action and therefore has a low probability of generating resistance. Such properties make PACT ideally suited for utilization in localized applications such as burn wounds. The aim of this study was to determine the antimicrobial activity of MB and temoporfin against both a S. aureus isolate and a P. aeruginosa isolate in light (640 nm) and dark conditions at a range of time points (0–20 min). A Staphylococcus aureus isolate and a Pseudomonas aeruginosa isolate were treated in vitro with methylene blue (MB) and temoporfin under different conditions following exposure to light at 640 nm and in no-light (dark) conditions. Bacterial cell viability [colony-forming units (c.f.u.) ml−1] was then calculated. Against P. aeruginosa , when MB was used as the photosensitizer, no phototoxic effect was observed in either light or dark conditions. After treatment with temoporfin, a reduction of less than one log (7.00×107 c.f.u. ml−1) was observed in the light after 20 min of exposure. However, temoporfin completely eradicated S. aureus in both light and dark conditions after 1 min (where a seven log reduction in c.f.u. ml−1 was observed). Methylene blue resulted in a loss of S. aureus viability, with a two log reduction in bacterial viability (c.f.u. ml−1) reported in both light and dark conditions after 20 min exposure time. Temoporfin demonstrated greater antimicrobial efficacy than MB against both the S. aureus and P. aeruginosa isolates tested. At 12.5 µM temoporfin resulted in complete eradication of S. aureus . In light of this study, further research into the validity of PACT, coupled with the photosensitizers (such as temoporfin), should be conducted in order to potentially develop alternative antimicrobial treatment regimes for burn wounds.

Antimicrobial chemotherapy of patients with lymphadenitis and adenophlegmon of the maxillofacial region

Relevance. Patients with maxillofacial lymphadenitis account for 3.09 % of the total number of hospitalized in specialized departments of maxillofacial surgery, and 5.7% of the number of patients with various inflammatory processes of the maxillofacial region.Aim. Microbiological substantiation of the algorithm of antimicrobial chemotherapy for lymphadenitis and adenophlegmon of the maxillofacial region.Materials and methods. The analysis of the results of microbiological studies and determination of the sensitivity of isolated microorganisms to antibiotics of the material from inflammatory foci in lymphadenitis and adenophlegmon of the maxillofacial region was carried out using a standard protocol of laboratory microbiological studies. Anaerobic bacteria were cultured in the HiAnaerobic System Mark III anaerostat, identification was carried out using Biochemical Identification Test Kits (Himedia Labs).Results. The results of determining the sensitivity of the main pathogens of limphadenitis and adenophlegmon to the most commonly used antibiotics: groups of beta- lactam drugs, macrolides, lincosamides, imidazoles, teracyclines and fluoroquinolones are presented. The priorities of prescribing different treatment regimens are determined, taking into account the international classification of antibiotics AWaRe, adopted by WHO in 2018.Conclusions. Recommended drugs of choice for various forms of lymphadenitis and adenoflegmon include combinations of amoxicillin with clavulanic acid, lincosamides (preferably clindamycin) and fluoroquinolones (ciprofloxacin), which should be combined with imidazoles in odontogenic limphadenitis and adenophlegmon (for example, tinidazole as part of the complex drug Tsifran ST).