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233900.9420Phenotypic ESBL and non-phenotypic ESBL isolates of Klebsiella pneumoniae exhibit differing responses to induced antimicrobials resistance and subsequent antibiotic cross-resistance. AIM: To investigate the effect of adapting Klebsiella pneumoniae clinical isolates harboring ESBL genes to cetrimide (CT) in terms of subsequent cross-resistance to other biocides and antibiotics, and to investigate changes to virulence markers, such as biofilm formation and efflux activity. The changes between phenotypic extended spectrum β-lactamases (pESBL) expressing isolates and non-phenotypic ESBL (npESBL) isolates was compared. METHODS AND RESULTS: Kl. pneumoniae isolates (14 pESBL and 17 npESBL) were adapted to increasing concentrations of CT, until 4 × MIC was reached. The MIC of the adapted isolates was tested against chloroxylenol (CX) and chlorhexidine. Disk diffusion techniques were used to determine the susceptibility of the isolates to different antibiotics. Biofilm formation was assessed for the isolates using the crystal violet method and efflux pump activity was studied using the ethidium bromide assay. After CT adaptation, 100% of npESBL isolates and 85.7% of pESBL isolates showed increase in CT MIC after CT adaptation. While 41.2% of npESBL and 57.1% of the pESBL isolates showed a cross-resistance with chlorhexidine. CT adaptation resulted in a significant decrease in the susceptibility of npESBL isolates to aztreonam and cefotaxime compared to pESBL isolates, which could be linked to the increase in efflux activity of npESBL compared to pESBL. Biofilm formation was significantly increased after CT adaptation regardless of the type of isolate. CONCLUSIONS: The extensive use of biocides in the environment can induce cross-resistance to other biocides and antibiotics, and can increase the ability of bacteria to form biofilms. The response of bacteria to biocide adaptation differs between pESBL and npESBL isolates, although the effect is strain specific.202336724268
233810.9387Characterization of disinfectant susceptibility profiles among clinical isolates of Acinetobacter baumannii in Ardabil, Iran. Antimicrobial disinfectants have been extensively used to control hospital-acquired infections worldwide. Prolonged exposure to bacteria could promote resistance to antimicrobial disinfectants. This study evaluated the antimicrobial activity of four commonly used disinfectants; triclosan, chlorhexidine digluconate, benzalkonium chloride, and formaldehyde against Acinetobacter baumannii clinical isolates. This study also determined the prevalence and association of efflux pumps encoding genes qacE, qacED1, emrA, and aceI with tolerance to disinfectants. A total of 100 A. baumannii isolates were included in the current study. The antimicrobial disinfectants' minimum inhibitory concentration (MIC) was determined using an agar dilution method. Genes involved in resistance to disinfectants were investigated by PCR method. The benzalkonium chloride MICs ranged between 32 and 128 μg mL-1, chlorhexidine digluconate 8-64 μg mL-1, triclosan 1-32 μg mL-1, and formaldehyde 128 μg mL-1. Overall, the highest MIC90 value was identified for formaldehyde (128 μg mL-1), followed by benzalkonium chloride and chlorhexidine digluconate (64 μg mL-1, each one) and triclosan (4 μg mL-1). In the present study, the qacE, qacED1, emrA, and aceI genes were found in 91%, 55%, 100%, and 88% of isolates, respectively. The qacG gene was not identified in our A. baumannii isolates. The qacED1 gene was associated with higher MICs for all disinfectants tested (P < 0.05), while the qacE and aceI genes were associated with higher MICs for benzalkonium chloride and chlorhexidine. This study indicated that triclosan is the most effective disinfectant against A. baumannii isolates.202338063878
233720.9386Klebsiella pneumoniae susceptibility to biocides and its association with cepA, qacΔE and qacE efflux pump genes and antibiotic resistance. BACKGROUND: Although antiseptics are some of the most widely used antibacterials in hospitals, there is very little information on reduced susceptibility to these biocides and its relationship with resistance to antibiotics. AIM: To determine the relationship between reduced susceptibility to biocides and the carriage of antiseptic resistance genes, cepA, qacΔE and qacE, as well as identifying the role of efflux pumps in conferring reduced susceptibility. METHODS: Susceptibility was assessed for five biocides: chlorhexidine, benzalkonium chloride, Trigene, MediHex-4, Mediscrub; and for 11 antibiotics against 64 isolates of Klebsiella pneumoniae. Susceptibility to all compounds was tested by the agar double dilution method (DDM) and the effect of efflux pumps on biocides determined by repeating the susceptibility studies in the presence of the efflux pump inhibitor carbonyl cyanide m-chlorophenyl hydrazone (CCCP). The presence of the cepA, qacΔE and qacE genes was identified by polymerase chain reaction. FINDINGS: The bacteria were not widely antibiotic resistant though a few showed reduced susceptibility to cefoxitin, chloramphenicol and rifampicin and later-generation cephalosporins but not to carbapenems. Biocide susceptibility, tested by DDM, showed that 50, 49 and 53 strains had reduced susceptibility to chlorhexidine, Trigene and benzalkonium chloride, respectively. The antiseptic resistance genes cepA, qacΔE and qacE were found in 56, 34 and one isolates respectively and their effects as efflux pumps were determined by CCCP (10 mg/L), which decreased the minimum inhibitory concentrations (MICs) of chlorhexidine and Medihex-4 by 2-128-fold but had no impact on the MICs of benzalkonium chloride, Trigene and Mediscrub. CONCLUSION: There was a close link between carriage of efflux pump genes, cepA, qacΔE and qacE genes and reduced biocide susceptibility, but not antibiotic resistance, in K. pneumoniae clinical isolates.201222498639
619030.9374Identifying Escherichia coli genes involved in intrinsic multidrug resistance. Multidrug resistance is a major cause of clinical failure in treating bacterial infections. Increasing evidence suggests that bacteria can resist multiple antibiotics through intrinsic mechanisms that rely on gene products such as efflux pumps that expel antibiotics and special membrane proteins that block the penetration of drug molecules. In this study, Escherichia coli was used as a model system to explore the genetic basis of intrinsic multidrug resistance. A random mutant library was constructed in E. coli EC100 using transposon mutagenesis. The library was screened by growth measurement to identify the mutants with enhanced or reduced resistance to chloramphenicol (Cm). Out of the 4,000 mutants screened, six mutants were found to be more sensitive to Cm and seven were more resistant compared to the wild-type EC100. Mutations in 12 out of the 13 mutants were identified by inverse polymerase chain reaction. Mutants of the genes rob, garP, bipA, insK, and yhhX were more sensitive to Cm compared to the wild-type EC100, while the mutation of rhaB, yejM, dsdX, nagA, yccE, atpF, or htrB led to higher resistance. Overexpression of rob was found to increase the resistance of E. coli biofilms to tobramycin (Tob) by 2.7-fold, while overexpression of nagA, rhaB, and yccE significantly enhanced the susceptibility of biofilms by 2.2-, 2.5-, and 2.1-fold respectively.200818807027
227440.9368Contribution of genetic factors towards cefotaxime and ciprofloxacin resistance development among Extended spectrum beta-lactamase producing-Quinolone resistant pathogenic Enterobacteriaceae. β-lactams and quinolones are widely utilised to treat pathogenic Enterobacterial isolates worldwide. Due to improper use of these antibiotics, both ESBL producing and quinolone resistant (ESBL-QR) pathogenic bacteria have emerged. Nature of contribution of beta-lactamase (bla)/quinolone resistant (QR) genes, efflux pumps (AcrAB-TolC) over-expression and outer membrane proteins (OMPs) /porin loss/reduction and their combinations towards development of this phenotype were explored in this study. Kirby-Bauer disc diffusion method was used for phenotypic characterization of these bacteria and minimum inhibitory concentration of cefotaxime and ciprofloxacin was determined by broth micro dilution assay. Presence of bla, QR, gyrA/B genes was examined by PCR; acrB upregulation by real-time quantitative PCR and porin loss/reduction by SDS-PAGE. Based on antibiogram, phenotypic categorization of 715 non-duplicate clinical isolates was: ESBL(+)QR(+) (n = 265), ESBL(+)QR(-) (n = 6), ESBL(-)QR(+) (n = 346) and ESBL(-)QR(-)(n = 11). Increased OmpF/K35 and OmpC/K36 reduction, acrB up-regulation, prevalence of bla, QR genes and gyrA/B mutation was observed among the groups in following order: ESBL(+)QR(+)> ESBL(-)QR(+)> ESBL(+)QR-> ESBL(-)QR(-). Presence of bla gene alone or combined porin loss and efflux pump upregulation or their combination contributed most for development of a highest level of cefotaxime resistance of ESBL(+)QR(+) isolates. Similarly, combined presence of QR genes, porin loss/reduction, efflux pump upregulation and gyrA/B mutation contributed towards highest ciprofloxacin resistance development of these isolates.202437884102
209750.9365Effective Photodynamic Therapy with Ir(III) for Virulent Clinical Isolates of Extended-Spectrum Beta-Lactamase Klebsiella pneumoniae. BACKGROUND: The extended-spectrum beta-lactamase (ESBL) Klebsiella pneumoniae is one of the leading causes of health-associated infections (HAIs), whose antibiotic treatments have been severely reduced. Moreover, HAI bacteria may harbor pathogenic factors such as siderophores, enzymes, or capsules, which increase the virulence of these strains. Thus, new therapies, such as antimicrobial photodynamic inactivation (aPDI), are needed. METHOD: A collection of 118 clinical isolates of K. pneumoniae was characterized by susceptibility and virulence through the determination of the minimum inhibitory concentration (MIC) of amikacin (Amk), cefotaxime (Cfx), ceftazidime (Cfz), imipenem (Imp), meropenem (Mer), and piperacillin-tazobactam (Pip-Taz); and, by PCR, the frequency of the virulence genes K2, magA, rmpA, entB, ybtS, and allS. Susceptibility to innate immunity, such as human serum, macrophages, and polymorphonuclear cells, was tested. All the strains were tested for sensitivity to the photosensitizer PSIR-3 (4 µg/mL) in a 17 µW/cm(2) for 30 min aPDI. RESULTS: A significantly higher frequency of virulence genes in ESBL than non-ESBL bacteria was observed. The isolates of the genotype K2+, ybtS+, and allS+ display enhanced virulence, since they showed higher resistance to human serum, as well as to phagocytosis. All strains are susceptible to the aPDI with PSIR-3 decreasing viability in 3log10. The combined treatment with Cfx improved the aPDI to 6log10 for the ESBL strains. The combined treatment is synergistic, as it showed a fractional inhibitory concentration (FIC) index value of 0.15. CONCLUSIONS: The aPDI effectively inhibits clinical isolates of K. pneumoniae, including the riskier strains of ESBL-producing bacteria and the K2+, ybtS+, and allS+ genotype. The aPDI with PSIR-3 is synergistic with Cfx.202133922077
247860.9364Study on the resistance mechanism via outer membrane protein OprD2 and metal β-lactamase expression in the cell wall of Pseudomonas aeruginosa. The aim of the present study was to evaluate the imipenem-resistant mechanism via the outer membrane protein (OMP) OprD2 and metal β-lactamase expression in the cell wall of Pseudomonas aeruginosa. The Pseudomonas aeruginosa was clinically separated and validated by VITEK-2 full-automatic bacteria analyzer. Drug resistance, sensitive antibiotics and minimum inhibitory concentration (MIC) were tested using the drug sensitivity analysis system. The phenotype positive strains of MBL genes were screened using the Kirby-Bauer diffusion method by adding metal ion-chelating agent EDTA on the imipenem susceptibility paper. IMP-1, VIM-1 and SPM metaloenzyme genes were tested by polymerase chain reaction (PCR)-telomeric repeat amplification protocol (TRAP). The OMP OprD2 genes were tested by PCR-TRAP, and the protein expression was tested using western blot analysis. The location of OMP OprD2 was confirmed using the sodium salicylate inhibition test. The results showed that 80 portions (40%) of MBL-positive strains were screened out of 200 specimens. Imipenem-resistant Pseudomonas aeruginosa (IRPA) and MIC values were significantly higher than quality control bacteria and control bacteria (P<0.05). A total of 35 cases with IMP-1 positive, 20 with VIM-1 positive, 16 with SPM positive, 5 with 2 positive genes and 4 with 3 positive genes were screened among MBL positive strains. A total of 150 portions (75%) of OprD2 deficiencies were screened from 200 specimens. The standard strains and sensitive strains showed OprD2 protein bands at 45 kDa while no OprD2 protein bands appeared in OprD2 deficiency strains. It was in accordance with gene detection. In conclusion, OMP OprD2 deficiency and MBL phenotype positivity may be important mechanisms of IRPA.201627882088
229970.9364Determining the resistance of carbapenem-resistant Klebsiella pneumoniae to common disinfectants and elucidating the underlying resistance mechanisms. INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is a serious problem in hospitals worldwide, posing a particular risk to immunocompromised patients. Elimination strategies may prevent these drug-resistant bacteria from spreading within hospital environments. Here, the susceptibility of patient-derived CRKP strains to common chemical disinfectants and possible correlations between the presence of drug-resistance genes and increased resistance to disinfectants were investigated. METHODS: The minimum inhibitory (MIC) and the minimum bactericidal concentrations (MBC) of common chemical disinfectants against each CRKP strain were determined using agar dilution; K. pneumoniae ATCC700603 served as a standard. The presence of the drug-resistance genes qacΔE, qacA, acrA and qacE was determined using PCR. RESULTS: A total of 27 clinically isolated CRKP strains collected in our hospital from 2011 to 2013 exhibited sensitivity to the following common chemical disinfectants in decreasing order of sensitivity: 75% ethyl alcohol > 2% glutaraldehyde > "84" disinfectant > 0.2% benzalkonium bromide > 2% iodine tincture > 1% iodophor > 0.1% chlorhexidine acetate. Of the 27 strains, 59, 41, 19 and 15% contained qacΔE, qacA, acrA and qacE resistance genes; 15% carried acrA, qacΔE and qacA, and 26% carried both qacA and qacΔE. Comparative analysis indicated that drug-resistance genes were correlated with higher MIC values. CONCLUSION: These pan-resistant pathogenic CRKP strains contained various drug-resistance genes and exhibited relatively high resistance to ethyl alcohol, chlorhexidine acetate and iodophor. Monitoring the drug-resistance rates of CRKP strains displaying disinfectant resistance may facilitate appropriate and effective sterilisation and thus preventing the spread of these pan-resistant strains.201526184804
209580.9362In vitro activity of plazomicin against quinolone-resistant gram-negative bacteria isolated from catheter-associated urinary tract infections. Quinolone resistance among uropathogens is an increasing concern. Plazomicin is a new aminoglycoside that shows promising results against resistant bacteria. However, no study has yet tested its effect specifically on quinolone-resistant organisms. This study aimed to evaluate the in vitro activity of plazomicin and comparator drugs against quinolone-resistant Gram-negative isolates of catheter-associated urinary tract infections (CAUTI). Plazomicin demonstrated high inhibiting activity against Enterobacteriaceae isolates (95.9% at MIC≤ 2 mg/L), with MIC(50/90) was 1/2 mg/L. High MICs values were detected against non-Enterobacteriaceae isolates (MIC(50/90), 4/32 mg/L). Plazomicin had susceptibility rate of 97.2% against Enterobacteriaceae isolates carrying aminoglycosides modifying enzymes (AME) genes, while other aminoglycosides, amikacin and gentamicin showed reduced activity (32.4% and 25.4%, respectively). In conclusion, plazomicin showed potent in vitro activity against quinolone-resistant Enterobacteriaceae causing CAUTI, regardless of the AME pattern.202133810779
622390.9359Bicarbonate induces high-level resistance to the human antimicrobial peptide LL-37 in Staphylococcus aureus small colony variants. OBJECTIVES: Staphylococcus aureus small colony variants (SCVs) cause persistent infections and are resistant to cationic antibiotics. Antimicrobial peptides (AMPs) have been suggested as promising alternatives for treating antibiotic-resistant bacteria. We investigated the capacity of the human cationic AMP LL-37 to kill SCVs in the presence of physiological concentrations of bicarbonate, which are reported to alter bacterial membrane permeability and change resistance of bacteria to AMPs. METHODS: MBCs of LL-37 for S. aureus SCVs with mutations in different genes in the presence and absence of bicarbonate were determined. RESULTS: In the absence of bicarbonate, SCVs of S. aureus strains LS-1 and 8325-4 had the same level of resistance to LL-37 as the parental strain (8 mg/L). In the presence of bicarbonate, hemB, menD and aroD SCVs of LS-1 had high-level resistance to LL-37 (≥128 mg/L) compared with the parental strain (16 mg/L). However, only the aroD SCV of strain 8324-5 showed high-level resistance. 8325-4 harbours mutations in two genes, tcaR and rsbU, which are involved in antimicrobial sensing and the stress response, respectively. When rsbU was repaired in 8325-4 it displayed high-level resistance to LL-37 in the presence of bicarbonate. This phenotype was lost when tcaR was also repaired, demonstrating that RsbU and TcaR are involved in LL-37 resistance in the presence of bicarbonate. CONCLUSIONS: S. aureus SCVs would be resistant to high concentrations of LL-37 in niches where there are physiological concentrations of bicarbonate and therefore this AMP may not be effective in combating SCVs.201829211886
6371100.9359Bioactive compounds from the African medicinal plant Cleistochlamys kirkii as resistance modifiers in bacteria. Cleistochlamys kirkii (Benth) Oliv. (Annonaceae) is a medicinal plant traditionally used in Mozambique to treat infectious diseases. The aim of this study was to find resistance modifiers in C. kirkii for Gram-positive and Gram-negative model bacterial strains. One of the most important resistance mechanisms in bacteria is the efflux pump-related multidrug resistance. Therefore, polycarpol (1), three C-benzylated flavanones (2-4), and acetylmelodorinol (5) were evaluated for their multidrug resistance-reverting activity on methicillin-susceptible and methicillin-resistant Staphylococcus aureus and Escherichia coli AG100 and AG100 A strains overexpressing and lacking the AcrAB-TolC efflux pump system. The combined effects of antibiotics and compounds (2 and 4) were also assessed by using the checkerboard microdilution method in both S. aureus strains. The relative gene expression of the efflux pump genes was determined by real-time reverse transcriptase quantitative polymerase chain reaction. The inhibition of quorum sensing was also investigated. The combined effect of the antibiotics and compound 2 or 4 on the methicillin-sensitive S. aureus resulted in synergism. The most active compounds 2 and 4 increased the expression of the efflux pump genes. These results suggested that C. kirkii constituents could be effective adjuvants in the antibiotic treatment of infections.201829464798
2094110.9357Evaluation of the antibacterial activity of Weissella confusa K3 cell-free supernatant against extended-spectrum βeta lactamase (ESBL) producing uropathogenic Escherichia coli U60. Different strategies have been approved for controlling extended-spectrum βeta lactamase (ESBL) producing uropathogenic bacteria. The antibacterial activity of Lactic acid bacteria (LAB) is an effective strategy due to its probiotic characteristics and beneficial effects on human health. The antibiotic susceptibility test, disk diffusion method, and double disc synergy test indicated that five enteric uropathogenic isolates were ESBL producers during the present study. They recorded diameters of inhibition zones as ≤ 18, ≤ 8, ≤ 19, and ≤ 8 mm against cefotaxime (CTX), ceftazidime (CAZ), aztreonam (ATM), and ceftriaxone (CRO). Genotypically, bla(TEM) genes are the most common, with (100 %) occurrence in all the five enteric tested uropathogens, followed by bla(SHV) and bla(CTX) genes (60 %). In addition, out of 10 LAB isolates from dairy products, the CFS of isolate no. K3 had high antibacterial activity against the tested ESBLs, especially no. U60, with a MIC of 600 µl. Additionally, the MIC and sub-MIC of K3 CFS inhibited the production of antibiotic-resistant bla (TEM) genes of U60. Analyzing the 16S rRNA sequence confirmed that the most potent ESBL-producing bacteria (U60) and LAB (K3) isolates were identified as Escherichia coli U60.1 and Weissella confuse K3 with accession numbers MW173246 and MW173299.1, respectively, in GenBank.202336873575
8717120.9356Protective Effect of Pediococcus pentosaceus Li05 on Constipation via TGR5/TPH1/5-HT Activation. Pediococcus pentosaceus Li05, a strain of lactic acid bacteria isolated from the faeces of healthy volunteers, exhibited potential protective effects against various diseases. This study performed third-generation sequencing and detailed characterisation of its genome. The Li05 chromosome harboured conserved genes associated with acid resistance (atp), bile salt resistance (bsh), oxidative stress resistance (hsl, dltA, and et al.), and adhesion (nrd, gap, and et al.), whereas the plasmid did not contain antibiotic resistance or virulence genes. Following intervention with Li05 in loperamide-induced constipated mice, constipation symptoms improved. Meanwhile, alterations in gut microbiota, increased BSH activity in faeces, and modifications to the faecal bile acid profile were observed. Additionally, expression levels of TGR5 and TPH1 in the colon of the mice increased, leading to elevated 5-HT levels. When the TGR5 gene was knocked out or the TPH1 inhibitor LX1606 was administered to suppress 5-HT synthesis in constipated mice, the beneficial effects of Li05 on gastrointestinal motility and mucus secretion were reversed. Culturing intestinal organoids demonstrated that increased bile acids such as DCA, Iso-LCA, and EALCA could enhance 5-HT levels through the TGR5/TPH1 axis. Therefore, we concluded that Li05 regulated bile acid metabolism, subsequently increasing 5-HT levels through the TGR5/TPH1 axis, thus alleviating constipation.202541159760
5063130.9355Antibiotic resistance ofKlebsiella pneumoniae through β-arrestin recruitment-induced β-lactamase signaling pathway. Overuse and misuse of antibiotics leads to rapid evolution of antibiotic-resistant bacteria and antibiotic resistance genes. Klebsiella pneumoniae has become the most common pathogenic bacterium accountable for nosocomial infections due to its high virulence factor and general occurrence of resistance to most antibiotics. The β-lactamase signaling pathway has been suggested to be involved in antibiotic resistance against β-lactams in Klebsiella pneumoniae. In the present study, the molecular mechanism of the antibiotic resistance of Klebsiella pneumoniae was investigated and the results indicated involvement of the β-arrestin recruitment-induced β-lactamase signaling pathway. Antimicrobial susceptibility of Klebsiella pneumoniae was assessed using automated systems and extended-spectrum β-lactamase (ESBL) and β-arrestin expression levels in Klebsiella pneumoniae were analyzed by reverse-transcription quantitative PCR. β-lactam resistance in Klebsiella pneumoniae was determined using β-lactam agar screening plates. The results demonstrated that β-arrestin recruitment was increased in Klebsiella pneumoniae with antibiotic resistance (AR-K.P.) compared with that in the native Klebsiella pneumoniae strain (NB-K.P.). Increased production of ESBL was observed in AR-K.P. after treatment with the β-lactam penicillin. Of note, inhibition of β-arrestin recruitment significantly suppressed ESBL expression in AR-K.P. and in addition, genes encoding β-arrestin and ESBL were upregulated in Klebsiella pneumoniae. Restoration of endogenous β-arrestin markedly increased antibiotic resistance of Klebsiella pneumoniae to β-lactam. Knockdown of endogenous β-arrestin downregulated antibiotic resistance genes and promoted the inhibitory effects of β-lactam antibiotic treatment on Klebsiella pneumoniae growth. In conclusion, the present study identified that β-arrestin recruitment was associated with growth and resistance to β-lactams, which suggested that β-arrestin regulating ESBL expression may be a potential target for addressing antibiotic resistance to β-lactams in Klebsiella pneumoniae.201829563975
5748140.9354Nosocomial Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus: Sensitivity to Chlorhexidine-Based Biocides and Prevalence of Efflux Pump Genes. The widespread use of disinfectants and antiseptics has led to the emergence of nosocomial pathogens that are less sensitive to these agents, which in combination with multidrug resistance (MDR) can pose a significant epidemiologic risk. We investigated the susceptibility of nosocomial Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus to a 0.05% chlorhexidine (CHX) solution and a biocidal S7 composite solution based on CHX (0.07%) and benzalkonium chloride (BAC, 0.055%). The prevalence of efflux pump genes associated with biocide resistance and their relationship to antibiotic resistance was also determined. Both biocides were more effective against Gram-positive S. aureus than Gram-negative bacteria. The most resistant strains were P. aeruginosa strains, which were mainly killed by 0.0016% CHX and by 0.0000084% (CHX)/0.0000066% (BAC) S7. The S7 bactericidal effect was observed on P. aeruginosa and S. aureus after 10 min, while the bactericidal effect of CHX was only observed after 30 min. qacEΔ1 and qacE efflux pump genes were prevalent among E. coli and K. pneumoniae, while mexB was more often detected in P. aeruginosa. norA, norB, mepA, mdeA, and sepA were prevalent in S. aureus. The observed prevalence of efflux pump genes highlights the potential problem whereby the sensitivity of bacteria to biocides could decline rapidly in the future.202539796210
2459150.9354In vitro antimicrobial activity and resistance mechanisms of cefiderocol against clinical carbapenem-resistant gram-negative bacteria. BACKGROUND: The rise of carbapenem-resistant gram-negative bacteria (CRGNB) necessitates new therapeutic options such as cefiderocol. OBJECTIVE: To evaluate the in vitro efficacy of cefiderocol against clinical CRGNB and investigate associated resistance mechanisms. METHODS: A total of 370 CRGNB isolates were analyzed. Minimum inhibitory concentration (MIC) values were determined, and whole genome sequencing, efflux pump inhibition assays, and RT-qPCR were conducted to assess resistance-related mutations, gene loss, and expression changes. RESULTS: Cefiderocol demonstrated potent in vitro activity, with high susceptibility rates in C. freundii (100%), K. pneumoniae (93.3%), and E. hormaechei (92.2%), and notable activity against P. aeruginosa (80.0%) and Escherichia coli (76.8%). Efflux pump inhibition by Carbonyl Cyanide m-Chlorophenyl Hydrazone (CCCP) significantly reduced MICs in resistant strains. Key resistance mechanisms included β-lactamase gene variants (bla (OXA-66), bla (OXA-23), bla (SHV-12)), mutations in envZ, cirA, nuoC, ampC, and loss or altered expression of iron transporter genes (piuA, pirA, fepA). CONCLUSION: Cefiderocol is highly effective against CRGNB; however, resistance may arise through diverse mechanisms, including efflux pump activity. Continued surveillance of emerging resistance is essential to guide its optimal clinical use.202541113641
2340160.9354Binary CuO\CoO nanoparticles inhibit biofilm formation and reduce the expression of papC and fimH genes in multidrug-resistant Klebsiella oxytoca. BACKGROUND AND AIM: Binary copper-cobalt oxide nanoparticles (CuO\CoO NPs) are modern kinds of antimicrobials, which may get a lot of interest in clinical application. This study aimed to detect the effect of the binary CuO\CoO NPs on the expression of papC and fimH genes in multidrug-resistant (MDR) isolates of Klebsiella oxytoca to reduce medication time and improve outcomes. METHODS: Ten isolates of K. oxytoca were collected and identified by different conventional tests besides PCR. Antibiotic sensitivity and biofilm-forming ability were carried out. The harboring of papC and fimH genes was also detected. The effect of binary CuO\CoO nanoparticles on the expression of papC and fimH genes was investigated. RESULTS: Bacterial resistance against cefotaxime and gentamicin was the highest (100%), while the lowest percentage of resistance was to amikacin (30%). Nine of the ten bacterial isolates had the ability to form a biofilm with different capacities. MIC for binary CuO\CoO NPs was 2.5 µg/mL. Gene expression of papC and fimH was 8.5- and 9-fold lower using the NPs. CONCLUSION: Binary CuO\CoO NPs have a potential therapeutic effect against infections triggered by MDR K. oxytoca strains due to the NPs-related downregulation ability on the virulence genes of K. oxytoca.202337269387
2298170.9353Burden of biocide resistance among multidrug-resistant bacteria isolated from various clinical specimens in a tertiary care hospital. BACKGROUND: Most studies on biocide resistance and its genetic determinants arise from environmental or food-borne microbial isolates and only a few from clinically relevant isolates. OBJECTIVES: This study determines the proportion of biocide resistance against five commonly used biocides and detects biocide resistance genes among MDR bacterial isolates using PCR. METHODS: Consecutive MDR isolates (n ​= ​180) were included (30 each of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, and Enterococcus species) from clinical specimens of various inpatient units at JIPMER. The isolates were challenged at 0.5,1 and 2 Macfarland (McF) inoculum with discrete dilutions of disinfectants. The minimum bactericidal concentrations (MBCs) for 70% Ethanol, 1.5% Cresol, 2% Glutaraldehyde, 1% Cetrimide, and 1% Chlorhexidine were determined for the isolates using ATCC reference strains as controls. PCR was performed targeting qac A/B, G; smr; and nfx B genes. RESULTS: For all biocides, MDR isolates had MBCs less than the maximum MBCs of ATCC strains. For MDR K. pneumoniae, A. baumannii, and P. aeruginosa, the highest MBCs of chlorhexidine and cetrimide were ≥75 and ​≥ ​150 ​μg/ml respectively at 0.5 McF inoculum; whereas these organisms grew at higher inoculum (2McF) even at commercially recommended biocidal concentration (1%) corresponding to 750 and 1500 ​μg/ml of chlorhexidine and cetrimide respectively. Meanwhile, the highest MBCs of MDR E. coli were 75 and 150 ​μg/ml for chlorhexidine and cetrimide respectively. Interestingly, the Gram-positive cocci survived the action of up to 35% ethanol. The nfxB and qacG genes were detected in 87% and 6.67% of MDR P. aeruginosa isolates respectively with no biocide resistance genes detected among the other organisms. CONCLUSIONS: Biocide dilutions challenged with higher inoculum indicated a narrow margin of effectiveness for certain biocides. Although a significant proportion of clinical MDR isolates of P. aeruginosa harbored biocide resistance genes, this finding had no phenotypic correlation.202337769586
8832180.9352Pharyngeal Pumping and Tissue-Specific Transgenic P-Glycoprotein Expression Influence Macrocyclic Lactone Susceptibility in Caenorhabditis elegans. Macrocyclic lactones (MLs) are widely used drugs to treat and prevent parasitic nematode infections. In many nematode species including a major pathogen of foals, Parascaris univalens, resistance against MLs is widespread, but the underlying resistance mechanisms and ML penetration routes into nematodes remain unknown. Here, we examined how the P-glycoprotein efflux pumps, candidate genes for ML resistance, can modulate drug susceptibility and investigated the role of active drug ingestion for ML susceptibility in the model nematode Caenorhabditis elegans. Wildtype or transgenic worms, modified to overexpress P. univalens PGP-9 (Pun-PGP-9) at the intestine or epidermis, were incubated with ivermectin or moxidectin in the presence (bacteria or serotonin) or absence (no specific stimulus) of pharyngeal pumping (PP). Active drug ingestion by PP was identified as an important factor for ivermectin susceptibility, while moxidectin susceptibility was only moderately affected. Intestinal Pun-PGP-9 expression elicited a protective effect against ivermectin and moxidectin only in the presence of PP stimulation. Conversely, epidermal Pun-PGP-9 expression protected against moxidectin regardless of PP and against ivermectin only in the absence of active drug ingestion. Our results demonstrate the role of active drug ingestion by nematodes for susceptibility and provide functional evidence for the contribution of P-glycoproteins to ML resistance in a tissue-specific manner.202133668460
6009190.9352Efflux pump inhibitor chlorpromazine effectively increases the susceptibility of Escherichia coli to antimicrobial peptide Brevinin-2CE. Aim: The response of E. coli ATCC8739 to Brevinin-2CE (B2CE) was evaluated as a strategy to prevent the development of antimicrobial peptide (AMP)-resistant bacteria. Methods: Gene expression levels were detected by transcriptome sequencing and RT-PCR. Target genes were knocked out using CRISPR-Cas9. MIC was measured to evaluate strain resistance. Results: Expression of acrZ and sugE were increased with B2CE stimulation. ATCC8739ΔacrZ and ATCC8739ΔsugE showed twofold and fourfold increased sensitivity, respectively. The survival rate of ATCC8739 was reduced in the presence of B2CE/chlorpromazine (CPZ). Combinations of other AMPs with CPZ also showed antibacterial effects. Conclusion: The results indicate that combinations of AMPs/efflux pump inhibitors (EPIs) may be a potential approach to combat resistant bacteria.202438683168