OBJECTIVES: To analyse characteristics of Clostridioides difficile PCR ribotype 176 clinical isolates from Poland, the Czech Republic and Slovakia with regard to the differences in its epidemiology. METHODS: Antimicrobial susceptibility testing and whole genome sequencing were performed on a selected group of 22 clonally related isolates as determined by multilocus variable-number tandem repeat analysis (n = 509). Heterologous expression and functional analysis of the newly identified methyltransferase were performed. RESULTS: Core genome multilocus sequence typing found 10-37 allele differences. All isolates were resistant to fluoroquinolones (gyrA_p. T82I), aminoglycosides with aac(6')-Ie-aph(2'')-Ia in six isolates. Erythromycin resistance was detected in 21/22 isolates and 15 were also resistant to clindamycin with ermB gene. Fourteen isolates were resistant to rifampicin with rpoB_p. R505K or p. R505K/H502N, and five to imipenem with pbp1_p. P491L and pbp3_p. N537K. PnimBG together with nimB_p. L155I were detected in all isolates but only five were resistant to metronidazole on chocolate agar. The cfrE, vanZ1 and cat-like genes were not associated with linezolid, teicoplanin and chloramphenicol resistance, respectively. The genome comparison identified six transposons carrying antimicrobial resistance genes. The ermB gene was carried by new Tn7808, Tn6189 and Tn6218-like. The aac(6')-Ie-aph(2'')-Ia were carried by Tn6218-like and new Tn7806 together with cfrE gene. New Tn7807 carried a cat-like gene. Tn6110 and new Tn7806 contained an RlmN-type 23S rRNA methyltransferase, designated MrmA, associated with high-level macrolide resistance in isolates without ermB gene. CONCLUSIONS: Multidrug-resistant C. difficile PCR ribotype 176 isolates carry already described and unique transposons. A novel mechanism for erythromycin resistance in C. difficile was identified.

• Klíčová slova
• Clostridioides difficile infection, epidemiology, macrolide resistance methyltransferase, whole genome sequencing,
• MeSH
• antibakteriální látky * farmakologie   MeSH
• bakteriální léková rezistence * MeSH
• bakteriální proteiny genetika   MeSH
• Clostridioides difficile * genetika   účinky léků   izolace a purifikace   klasifikace   MeSH
• genomové ostrovy * MeSH
• klostridiové infekce * mikrobiologie   epidemiologie   MeSH
• lidé MeSH
• methyltransferasy genetika   MeSH
• mikrobiální testy citlivosti MeSH
• mnohočetná bakteriální léková rezistence * genetika   MeSH
• multilokusová sekvenční typizace MeSH
• ribotypizace MeSH
• sekvenování celého genomu MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Polsko epidemiologie   MeSH
• Názvy látek
• antibakteriální látky * MeSH
• bakteriální proteiny MeSH
• methyltransferasy MeSH

BACKGROUND: Pseudomonas aeruginosa can proliferate in immunocompromised individuals, forming biofilms that increase antibiotic resistance. This bacterium poses a significant global health risk due to its resistance to human defenses, antibiotics, and various environmental stresses. The objective of this study was to evaluate the antibacterial, anti-biofilm, and anti-quorum sensing activities of galloylquinic acid compounds (GQAs) extracted from Copaifera lucens leaves against clinical isolates of multidrug-resistant (MDR) P. aeruginosa. We have investigated the optimal concentration of GQAs needed to eradicate preexisting biofilms and manage wound infections caused by P. aeruginosa, in vitro and in vivo. RESULTS: Our results revealed that GQAs exhibited 25-40 mm inhibition zone diameters, with 1-4 µg/mL MIC and 2-16 µg/mL MBC values. GQAs interfered with the planktonic mode of P. aeruginosa isolates, and significantly inhibited their growth in the pre-formed biofilm architecture, with MBIC80 and MBEC80 values of 64 µg/mL and 128 µg/mL, respectively. The anti-biofilm effect was confirmed by fluorescence staining and confocal microscopy which showed a dramatic reduction in the cell viability and the biofilm thickness (62.5%), after exposure to 128 µg/mL of GQAs in particular. The scanning electron micrographs showed that GQAs impaired biofilm and bacterial structures by interfering with the biomass and the exopolysaccharides forming the matrix. GQAs also interfered with virulence factors and bacterial motility, where 128 µg/mL of GQAs significantly (p < 0.05) reduced rhamnolipid, pyocyanin, and the swarming motility of the organism which play a vital role in the biofilm formation. GQAs downregulated 89% of the quorum-sensing genes (lasI and lasR, pqsA and pqsR) involved in the biofilm formation. CONCLUSION: GQAs demonstrate significant promise as novel and potent antibiofilm and antivirulence agents against clinical isolates of MDR P. aeruginosa, with substantial potential to enhance wound healing in biofilm-associated infections. This promising antibacterial action positions GQAs as a superior alternative for the treatment of biofilm-associated wound infections, with substantial potential to improve wound healing and mitigate the impact of persistent bacterial infections. CLINICAL TRIAL NUMBER: not applicable.

• Klíčová slova
• Pseudomonas aeruginosa, Anti-biofilm, Antibacterial, Galloylquinic acid compounds,
• MeSH
• antibakteriální látky * farmakologie   MeSH
• biofilmy * účinky léků   růst a vývoj   MeSH
• infekce v ráně * mikrobiologie   farmakoterapie   MeSH
• lidé MeSH
• listy rostlin chemie   MeSH
• mikrobiální testy citlivosti MeSH
• mnohočetná bakteriální léková rezistence účinky léků   MeSH
• myši MeSH
• pseudomonádové infekce * mikrobiologie   farmakoterapie   MeSH
• Pseudomonas aeruginosa * účinky léků   fyziologie   izolace a purifikace   MeSH
• quorum sensing * účinky léků   MeSH
• rostlinné extrakty farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• rostlinné extrakty MeSH

Mine aerosol poses a serious health threat due to its easy access to the human respiratory tract. Damage may be caused by the chemical composition of dust and the substances adsorbed on its surface, including microorganisms that potentially affect human health. Our proposed research aimed to isolate Staphylococcus aureus strains from coal mine bioaerosol and to assess its sensitivity towards selected antibiotics. Bioaerosol samples were collected in three underground hard coal mines located in Upper Silesia in southern Poland. Microbiological tests of the air samples were carried out according to standard microbiological techniques. All tested strains of Staphylococcus aureus were sensitive to oxacillin, which indicated the lack of methicillin-resistant isolates (MRSA) in the tested group. However, antibiotic resistance from macrolide and lincosamide groups was observed among certain strains. 10% of isolates were constitutive MLSB resistance, while 4% of strains were inductive MLSB resistance. Less than 1% of isolates were erythromycin-resistant and clindamycin-sensitive (MSB). Based on the Chi-square test, statistically significant differences were found in the frequency of MSB, MLSB inductive, and MLSB constitutive phenotypes. Almost 30% of the identified strains showed multi-antibiotic resistance. However, the Chi-square test did not reveal any statistically significant differences in the frequency of multidrug-resistant strains in the considered research areas. The analyses carried out constituted the first study related to the isolation and assessment of drug susceptibility of Staphylococcus aureus in the bioaerosol of hard coal mines. Identification of bioaerosol in underground coal mines is a key issue because, due to the presence of pathogens, it plays a significant role in limiting the spread of occupational diseases. For the health of miners, research into microbial communities benefits the promotion of microbiological control of mine air.

• Klíčová slova
• Bioaerosol, Drug sensitivity, Mining excavations, Respirable dust, Staphylococci,
• MeSH
• antibakteriální látky * farmakologie   MeSH
• bakteriální léková rezistence * MeSH
• lidé MeSH
• methicilin rezistentní Staphylococcus aureus izolace a purifikace   účinky léků   MeSH
• mikrobiální testy citlivosti MeSH
• mikrobiologie vzduchu * MeSH
• mnohočetná bakteriální léková rezistence MeSH
• Staphylococcus aureus * účinky léků   izolace a purifikace   MeSH
• těžba uhlí * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Polsko MeSH
• Názvy látek
• antibakteriální látky * MeSH

The diverse environmental distribution of Salmonella makes it a global source of human gastrointestinal infections. This study aimed to detect Salmonella spp. and explore their diversity and antimicrobial susceptibility patterns in clinical and environmental samples. Pre-enrichment, selective enrichment, and selective plating techniques were adopted for the Salmonella detection whereas the API 20E test and Vitek Compact 2 system were used to confirm the identity of isolates. Salmonella serovars were subjected to molecular confirmation by 16S rDNA gene sequencing. Disc diffusion method and Vitek 2 Compact system determined the antibiotic susceptibility of Salmonella serovars. Multiple antibiotic resistance index (MARI) was calculated to explore whether Salmonella serovars originate from areas with heavy antibiotic usage. Results depicted low Salmonella prevalence in clinical and environmental samples (3.5%). The main detected serovars included Salmonella Typhimurium, S. enteritidis, S. Infantis, S. Newlands, S. Heidelberg, S. Indian, S. Reading, and S. paratyphi C. All the detected Salmonella serovars (27) exhibited multidrug resistance to three or more antimicrobial classes. The study concludes that the overall Salmonella serovars prevalence was found to be low in environmental and clinical samples of Western Saudi Arabia (Makkah and Jeddah). However, antimicrobial susceptibility patterns of human and environmental Salmonella serovars revealed that all isolates exhibited multidrug-resistance (MDR) patterns to frequently used antibiotics, which might reflect antibiotic overuse in clinical and veterinary medicine. It would be suitable to apply and enforce rules and regulations from the One Health approach, which aim to prevent antibiotic resistance infections, enhance food safety, and improve human and animal health, given that all Salmonella spp. detected in this investigation were exhibiting MDR patterns.

• Klíčová slova
• Salmonella, 16S rDNA, Antimicrobial resistance, Clinical, Environmental,
• MeSH
• antibakteriální látky * farmakologie   MeSH
• DNA bakterií genetika   MeSH
• fylogeneze MeSH
• lidé MeSH
• mikrobiální testy citlivosti * MeSH
• mikrobiologie životního prostředí MeSH
• mnohočetná bakteriální léková rezistence * MeSH
• prevalence MeSH
• RNA ribozomální 16S * genetika   MeSH
• Salmonella enterica * účinky léků   genetika   izolace a purifikace   klasifikace   MeSH
• salmonelóza * mikrobiologie   epidemiologie   MeSH
• séroskupina * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Saudská Arábie epidemiologie   MeSH
• Názvy látek
• antibakteriální látky * MeSH
• DNA bakterií MeSH
• RNA ribozomální 16S * MeSH

The adherence of bladder uroepithelial cells, subsequent expression, and regulation of type 1 fimbrial genes (key mediator of attachment) in clinical multidrug-resistant uropathogenic Escherichia coli (MDR-UPECs) isolated from individuals with asymptomatic bacteriuria (ABU) remain unexplored till date. Therefore, this study aimed to investigate the underlying molecular mechanisms associated with the adherence of clinical MDR-ABU-UPECs to human a uroepithelial cell line (HTB-4), both in the absence and presence of D-Mannose. These investigations focused on phase variation, expression, and regulation of type 1 fimbriae and were compared to a prototype ABU-strain (E. coli 83972) and symptomatic MDR-UPECs. Discordant to the ABU prototype strain, MDR-ABU-UPECs exhibited remarkable adhesive capacity that was significantly reduced after D-mannose exposure, fairly like the MDR symptomatic UPECs. The type 1 fimbrial phase variation, determined by the fim switch analysis, asserted the statistically significant incidence of "both OFF and ON" orientation among the adherent MDR-ABU-UPECs with a significant reduction in phase-ON colonies post-D-mannose exposure, akin to the symptomatic ones. This was indicative of an operative and alternating type 1 fimbrial phase switch. The q-PCR assay revealed a coordinated action of the regulatory factors; H-NS, IHF, and Lrp on the expression of FimB and FimE recombinases, which further controlled the function of fimH and fimA genes in ABU-UPECs, similar to symptomatic strains. Therefore, this study is the first of its kind to provide an insight into the regulatory crosstalk of different cellular factors guiding the adhesion of ABU-UPECs to the host. Additionally, it also advocated for the need to accurately characterize ABU-UPECs.

• Klíčová slova
• Adhesive capacity, Asymptomatic uropathogenic Escherichia coli, FimBE recombinases, Symptomatic uropathogenic Escherichia coli, Type 1 fimbriae-regulating factors, Type 1 fimbrial phase variation,
• MeSH
• adheziny Escherichia coli genetika   metabolismus   MeSH
• bakteriální adheze * MeSH
• bakteriální fimbrie * genetika   metabolismus   MeSH
• bakteriurie mikrobiologie   MeSH
• buněčné linie MeSH
• epitelové buňky * mikrobiologie   MeSH
• infekce vyvolané Escherichia coli * mikrobiologie   MeSH
• lidé MeSH
• mannosa metabolismus   farmakologie   MeSH
• mnohočetná bakteriální léková rezistence * genetika   MeSH
• proteiny fimbrií * genetika   metabolismus   MeSH
• proteiny z Escherichia coli genetika   metabolismus   MeSH
• regulace genové exprese u bakterií MeSH
• uropatogenní Escherichia coli * genetika   účinky léků   izolace a purifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adheziny Escherichia coli MeSH
• mannosa MeSH
• proteiny fimbrií * MeSH
• proteiny z Escherichia coli MeSH

BACKGROUND: Multidrug-resistant (MDR) bacteria pose a significant challenge to the treatment of infectious diseases. Of particular concern are members of the Klebsiella pneumoniae species complex (KpSC), which are frequently associated with hospital-acquired infections and have the potential to spread outside hospitals via wastewaters. In this study, we aimed to investigate the occurrence and phylogenetic relatedness of MDR KpSC from patients with urinary tract infections (UTIs), hospital sewage, municipal wastewater treatment plants (mWWTPs) and surface waters and to evaluate the clinical relevance of the KpSC subspecies. METHODS: A total of 372 KpSC isolates resistant to third-generation cephalosporins and/or meropenem were collected from patients (n = 130), hospital sewage (n = 95), inflow (n = 54) and outflow from the mWWTPs (n = 63), river upstream (n = 13) and downstream mWWTPs (n = 17) from three cities in the Czech Republic. The isolates were characterized by antimicrobial susceptibility testing and whole-genome sequencing (Illumina). The presence of antibiotic resistance genes, plasmid replicons and virulence-associated factors was determined. A phylogenetic tree and single nucleotide polymorphism matrix were created to reveal the relatedness between isolates. RESULTS: The presence of MDR KpSC isolates (95%) was identified in all water sources and locations. Most isolates (99.7%) produced extended-spectrum beta-lactamases encoded by blaCTX-M-15. Resistance to carbapenems (5%) was observed mostly in wastewaters, but carbapenemase genes, such as blaGES-51 (n = 10), blaOXA-48 (n = 4), blaNDM-1 (n = 4) and blaKPC-3 (n = 1), were found in isolates from all tested locations and different sources except rivers. Among the 73 different sequence types (STs), phylogenetically related isolates were observed only among the ST307 lineage. Phylogenetic analysis revealed the transmission of this lineage from patients to the mWWTP and from the mWWTP to the adjacent river and the presence of the ST307 clone in the mWWTP over eight months. We confirmed the frequent abundance of K. pneumoniae (K. pneumoniae sensu stricto and K. pneumoniae subsp. ozaenae) in patients suffering from UTIs. K. variicola isolates formed only a minor proportion of UTIs, and K. quasipneumoniae was not found among UTIs isolates; however, these subspecies were frequently observed in hospital sewage communities during the first sampling period. CONCLUSION: This study provides evidence of the transmission and persistence of the ST307 lineage from UTIs isolates via mWWTPs to surface waters. Isolates from UTIs consisted mostly of K. pneumoniae. Other isolates of KpSC were observed in hospital wastewaters, which implies the impact of sources other than UTIs. This study highlights the influence of urban wastewaters on the spread of MDR KpSC to receiving environments.

• Klíčová slova
• Klebsiella spp. subspecies, bla CTX−M−15, Urinary tract infections, Wastewater treatment plants,
• MeSH
• antibakteriální látky * farmakologie   MeSH
• bakteriální proteiny genetika   MeSH
• beta-laktamasy * genetika   MeSH
• fylogeneze * MeSH
• infekce bakteriemi rodu Klebsiella * mikrobiologie   epidemiologie   MeSH
• infekce močového ústrojí mikrobiologie   epidemiologie   MeSH
• infekce spojené se zdravotní péčí mikrobiologie   epidemiologie   MeSH
• Klebsiella pneumoniae * účinky léků   genetika   izolace a purifikace   klasifikace   MeSH
• lidé MeSH
• mikrobiální testy citlivosti * MeSH
• mnohočetná bakteriální léková rezistence * MeSH
• nemocnice * MeSH
• odpadní voda * mikrobiologie   MeSH
• odpadní vody mikrobiologie   MeSH
• sekvenování celého genomu MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• antibakteriální látky * MeSH
• bakteriální proteiny MeSH
• beta-laktamasy * MeSH
• odpadní voda * MeSH
• odpadní vody MeSH

OBJECTIVES: We performed a retrospective analysis of MRSA isolates collected at the university equine clinic including clinical isolates from 2008 to 2021 and screening environmental, equine and personnel isolates from 2016. METHODS: Screening and clinical samples were cultured on Brilliance MRSA 2 and Columbia agar (Oxoid), respectively, with enrichment for environmental samples. Antimicrobial susceptibility was assessed by disc diffusion. All the isolates were characterized by spa typing. Eighteen selected isolates were subjected to WGS with subsequent wgMLST clonal analysis. RESULTS: Among 75 MRSA isolates, five spa types were identified, the majority (n = 67; 89.33%) was t011. All isolates were resistant to cefoxitin and ampicillin and carried the mecA gene. In addition, the isolates were resistant to tetracycline (n = 74; 98.67%), gentamicin (n = 70; 93.33%), enrofloxacin (n = 54; 72.00%), sulfamethoxazole-trimethoprim (n = 5; 6.67%) and lincomycin (n = 3; 4.00%) with corresponding genetic markers for the resistance detected in the sequenced isolates. All 18 sequenced isolates belonged to ST398, 16 carried SCCmec type IVa and two carried SCCmec type Vc (5C2&5). Further, isolates carried aur, hlgA, hlgB and hlgC virulence genes, and five isolates carried sak and scn genes, which are part of the immune evasion cluster. Close genetic relatedness was found between isolates from the staff of the clinic and clinical samples of horses. CONCLUSIONS: Repeated introduction and long-term persistence of the equine LA-MRSA subclone (ST398-MRSA-IVa/Vc(5C2&5), t011) among the infected horses at the equine clinic with the colonization of personnel, and the environment contamination that might contribute to transmission were observed.

• MeSH
• antibakteriální látky * farmakologie   MeSH
• bakteriální proteiny genetika   MeSH
• koně mikrobiologie   MeSH
• lidé MeSH
• methicilin rezistentní Staphylococcus aureus * genetika   izolace a purifikace   účinky léků   klasifikace   MeSH
• mikrobiální testy citlivosti * MeSH
• mikrobiologie životního prostředí MeSH
• mnohočetná bakteriální léková rezistence genetika   MeSH
• multilokusová sekvenční typizace MeSH
• nemoci koní mikrobiologie   MeSH
• nemocnice veterinární MeSH
• retrospektivní studie MeSH
• sekvenování celého genomu MeSH
• stafylokokové infekce * mikrobiologie   veterinární   epidemiologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• bakteriální proteiny MeSH

BACKGROUND: Febrile neutropenia (FN) is a common complication of stem cell transplantation. AIM: To evaluate the frequency of sepsis in patients with FN colonized with resistant Gram-negative bacteria (extended-spectrum β-lactamase (ESBL)-positive, multidrug-resistant (MDR) Pseudomonas aeruginosa) and the choice of primary antibiotic in colonized patients. METHODS: This retrospective study analysed data from patients undergoing haematopoietic stem cell transplantation from January 2018 to September 2022. Data were extracted from the hospital information system. FINDINGS: Carbapenem as the primary antibiotic of choice was chosen in 10.9% of non-colonized +/-AmpC patients, 31.5% of ESBL+ patients, and 0% of MDR P. aeruginosa patients. Patients with FN and MDR P. aeruginosa colonization had a high prevalence of sepsis (namely 100%, P = 0.0197). The spectrum of sepsis appeared to be different, with Gram-negative bacilli predominating in the ESBL+ group (OR: 5.39; 95% CI: 1.55-18.76; P = 0.0123). Colonizer sepsis was present in 100% of sepsis with MDR P. aeruginosa colonization (P = 0.002), all in allogeneic transplantation (P = 0.0003), with a mortality rate of 33.3% (P = 0.0384). The incidence of sepsis in patients with ESBL+ colonization was 25.9% (P = 0.0197), with colonizer sepsis in 50% of sepsis cases (P = 0.0002), most in allogeneic transplantation (P = 0.0003). CONCLUSION: The results show a significant risk of sepsis in FN with MDR P. aeruginosa colonization, a condition almost exclusively caused by the colonizer. At the same time, a higher risk of Gram-negative sepsis has been demonstrated in patients colonized with ESBL+ bacteria.

• Klíčová slova
• ESBL positive, Febrile neutropenia, Multidrug resistant, Stem cell transplantation,
• MeSH
• antibakteriální látky * terapeutické užití   MeSH
• dospělí MeSH
• febrilní neutropenie * mikrobiologie   MeSH
• gramnegativní bakteriální infekce * farmakoterapie   epidemiologie   MeSH
• gramnegativní bakterie * účinky léků   izolace a purifikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mnohočetná bakteriální léková rezistence MeSH
• přenašečství mikrobiologie   epidemiologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• sepse mikrobiologie   MeSH
• transplantace hematopoetických kmenových buněk škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH

Multidrug resistant (MDR) bacteria are recognized to be one of the most important problems in public health. The outer membrane permeability is a critical intrinsic mechanism of bacterial resistance. In addition, bacteria produce a small number of dormant persister cells causing multidrug tolerance that reduces antimicrobial efficacy. This study aimed to evaluate the inhibitory effects of the combination of aromatic isothiocyanates (ITCs) with membrane-active agents on bacterial persisters and MDR Gram-negative bacteria. Our study demonstrated that membrane-active agents, particularly ethylenediaminetetraacetic acid (EDTA) synergistically enhanced the inhibitory activity of aromatic benzyl ITC and phenethyl ITC against most Gram-negative bacteria strains with fractional inhibitory concentration index values ranging from 0.18 to 0.5 and 0.16 to 0.5, respectively, and contributed to an 8- to 64-fold minimal inhibitory concentration reduction compared with those of aromatic ITCs alone. The EDTA-aromatic ITCs combination effectively reduced the survival rates of tested bacteria and significantly eradicated bacterial persisters (p = 0.033 and 0.037, respectively). The growth kinetics analysis also supported the enhanced inhibitory effect of EDTA-aromatic ITCs combination against tested bacteria. Our results suggested an alternate treatment strategy against Gram-negative bacteria, promoting the entry of aromatic ITCs into bacterial cytoplasm to facilitate bacterial clearance and thus preventing the development of bacterial resistance.

• Klíčová slova
• Antimicrobial resistance, Isothiocyanates, Outer membrane permeability, Persistence, Synergy,
• MeSH
• antibakteriální látky * farmakologie   MeSH
• EDTA * farmakologie   MeSH
• gramnegativní bakterie * účinky léků   MeSH
• isothiokyanatany * farmakologie   MeSH
• mikrobiální testy citlivosti * MeSH
• mikrobiální viabilita účinky léků   MeSH
• mnohočetná bakteriální léková rezistence * účinky léků   MeSH
• permeabilita buněčné membrány účinky léků   MeSH
• synergismus léků MeSH
• vnější bakteriální membrána účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• EDTA * MeSH
• isothiokyanatany * MeSH

Multidrug-resistant (MDR) Staphylococcus aureus infections significantly threaten global health. With rising resistance to current antibiotics and limited solutions, the urgent discovery of new, effective, and affordable antibacterials with low toxicity is imperative to combat diverse MDR S. aureus strains. Hence, in this study, we introduce an in silico phytochemical-based approach for discovering novel antibacterial agents, underscoring the potential of computational approaches in therapeutic discovery. Glucomoringin Isothiocyanate (GMG-ITC) from Moringa oleifera Lam. is one of the phytochemical compounds with several biological activities, including antimicrobial, anti-inflammatory, and antioxidant activities, and is also effective against S. aureus. This study focuses on screening GMG-ITC as a potential drug candidate to combat MDR S. aureus infections through a molecular docking approach. Moreover, interaction amino acid analysis, in silico pharmacokinetics, compound target prediction, pathway enrichment analysis and molecular dynamics (MD) simulations were conducted for further investigation. Molecular docking and interaction analysis showed strong binding affinity towards S. aureus lipase, dihydrofolate reductase, and other MDR S. aureus proteins, including penicillin-binding protein 2a, MepR, D-Ala:D-Ala ligase, and RPP TetM, through hydrophilic and hydrophobic interactions. GMG-ITC also showed a strong binding affinity to cyclooxygenase-2 and FAD-dependent NAD(P)H oxidase, suggesting that it is a potential anti-inflammatory and antioxidant candidate that may eliminate inflammation and oxidative stress associated with S. aureus infections. MD simulations validated the stability of the GMG-ITC molecular interactions determined by molecular docking. In silico pharmacokinetic analysis highlights its potency as a drug candidate, showing strong absorption, distribution, and excretion properties in combination with low toxicity. It acts as an active protease and enzyme inhibitor with moderate activity against GPCR ligands, ion channels, nuclear receptor ligands, and kinases. Enrichment analysis further elucidated its involvement in important biological, molecular, and cellular functions with potential therapeutic applications in diseases like cancer, hepatitis B, and influenza. Results suggest that GMG-ITC is an effective antibacterial agent that could treat MDR S. aureus-associated infections.

• Klíčová slova
• GO and KEGG enrichment pathway, Glucomoringin isothiocyanate, In silico pharmacokinetic analysis, MD simulation, Molecular docking, Multi-drug resistance,
• MeSH
• antibakteriální látky * chemie   farmakologie   MeSH
• bakteriální proteiny antagonisté a inhibitory   chemie   metabolismus   MeSH
• fytonutrienty chemie   farmakologie   MeSH
• isothiokyanatany * chemie   farmakologie   MeSH
• lidé MeSH
• methicilin rezistentní Staphylococcus aureus účinky léků   MeSH
• mnohočetná bakteriální léková rezistence účinky léků   MeSH
• Moringa oleifera chemie   MeSH
• objevování léků MeSH
• počítačová simulace MeSH
• simulace molekulární dynamiky MeSH
• simulace molekulového dockingu * MeSH
• Staphylococcus aureus účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• bakteriální proteiny MeSH
• benzyl isothiocyanate MeSH Prohlížeč
• fytonutrienty MeSH
• isothiokyanatany * MeSH