-
Iranian Journal of Microbiology Apr 2024is an opportunistic pathogen causing nosocomial infections. Diclofenac is an anti-inflammatory drug that is considered a non-antibiotic drug. This study assessed the...
BACKGROUND AND OBJECTIVES
is an opportunistic pathogen causing nosocomial infections. Diclofenac is an anti-inflammatory drug that is considered a non-antibiotic drug. This study assessed the antibacterial and antibiofilm effects of diclofenac and levofloxacin/diclofenac combination against levofloxacin resistant isolates.
MATERIALS AND METHODS
Minimum inhibitory concentration was determined using broth microdilution method for levofloxacin, diclofenac, and levofloxacin/diclofenac combination. Biofilm forming capacity and biofilm inhibition assay were determined. Relative gene expression was measured for efflux pump genes; , and genes and biofilm related genes , and without and with diclofenac and the combination.
RESULTS
Diclofenac demonstrated MIC of 1 mg/ml. The combination-with ½ MIC diclofenac-showed synergism where levofloxacin MIC undergone 16-32 fold decrease. All the isolates that overexpressed and showed a significant decrease in gene expression in presence of diclofenac or the combination. The mean percentage inhibition of biofilm formation with diclofenac and the combination was 40.59% and 46.49%, respectively. This agreed with biofilm related genes expression investigations.
CONCLUSION
Diclofenac showed an antibacterial effect against The combination showed synergism, significant reduction in biofilm formation and in the relative level of gene expression. Furthermore, it can potentiate the levofloxacin activity or revert its resistance.
PubMed: 38854979
DOI: 10.18502/ijm.v16i2.15349 -
Journal of Infection in Developing... Jun 2023Stenotrophomonas maltophilia is a Gram-negative, opportunistic pathogen associated with a high morbidity and mortality rate. We report our clinical experience in...
INTRODUCTION
Stenotrophomonas maltophilia is a Gram-negative, opportunistic pathogen associated with a high morbidity and mortality rate. We report our clinical experience in treating a patient with infected pancreatic necrosis caused by multidrug-resistant (MDR) S. maltophilia with a novel drug combination.
CASE REPORT
A 65-year-old male with history of type II diabetes was admitted with acute pancreatitis, voluminous ascites, and signs of sepsis after undergoing an echo-endoscopy procedure with pancreas biopsy to investigate a Wirsung duct dilatation. Retroperitoneal fluid culture revealed S. maltophilia resistant to colistin and with intermediate susceptibility to trimethoprim-sulfamethoxazole and levofloxacin. The synergy between aztreonam (ATM) and ceftazidime/avibactam (CZA) was demonstrated using the combined disk pre-diffusion test.
CONCLUSIONS
There are sparse data providing guidance on the optimal regimen against MDR S. maltophilia infections. Although in this case a surgical excision was essential, combination of ATM and CZA provided effective synergistic antimicrobial treatment with clinical cure of severe acute pancreatitis infected with S. maltophilia. The combined disk pre-diffusion test with ATM and CZA requires no special equipment and can be routinely performed in clinical microbiology labs. Combination of ATM with CZA should be considered for cases of MDR S. maltophilia infections with limited treatment options.
Topics: Male; Humans; Aged; Aztreonam; Ceftazidime; Anti-Bacterial Agents; Stenotrophomonas maltophilia; Diabetes Mellitus, Type 2; Acute Disease; Pancreatitis; Drug Combinations; Microbial Sensitivity Tests; Gram-Negative Bacterial Infections
PubMed: 37406060
DOI: 10.3855/jidc.17290 -
Journal of Animal Science and... Dec 2023Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety. Our previous study found that...
BACKGROUND
Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety. Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in 'gastroenterogenic mastitis'. However, the mechanism has not been fully clarified. Recently, we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows, and the abundance of Stenotrophomonas maltophilia (S. maltophilia) was significantly increased in both the rumen and milk microbiota. Accordingly, we hypothesized that 'gastroenterogenic mastitis' can be induced by the migration of endogenous gut bacteria to the mammary gland. Therefore, this study investigated the mechanism by which enterogenic S. maltophilia induces mastitis.
RESULTS
First, S. maltophilia was labelled with superfolder GFP and administered to mice via gavage. The results showed that treatment with S. maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier, leading to intestinal inflammation and intestinal leakage. Furthermore, tracking of ingested S. maltophilia revealed that S. maltophilia could migrate from the gut to the mammary gland and induce mastitis. Subsequently, mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S. maltophilia. Then, using mouse mammary epithelial cells (MMECs), we verified that S. maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway.
CONCLUSIONS
In conclusion, the results showed that enterogenic S. maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis. Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.
PubMed: 38124149
DOI: 10.1186/s40104-023-00952-y -
Frontiers in Cellular and Infection... 2023is a multidrug-resistant (MDR) opportunistic pathogen with high resistance to most clinically used antimicrobials. The dissemination of MDR and difficult treatment of...
BACKGROUND
is a multidrug-resistant (MDR) opportunistic pathogen with high resistance to most clinically used antimicrobials. The dissemination of MDR and difficult treatment of its infection in clinical settings are global issues.
METHODS
To provide more genetic information on and find a better treatment strategy, we isolated five , SMYN41-SMYN45, from a Chinese community that were subjected to antibiotic susceptibility testing, biofilm formation assay, and whole-genome sequencing. Whole-genome sequences were compared with other thirty-seven sequences.
RESULTS
The five strains had similar antibiotic resistance profiles and were resistant to β-lactams, aminoglycosides, and macrolides. They showed similar antimicrobial resistance (AMR) genes, including various efflux pumps, β-lactamase resistance genes (), aminoglycoside resistance genes [, ], and macrolide-resistant gene (). Genome sequencing analysis revealed that SMYN41-SMYN45 belonged to sequence type 925 (ST925), ST926, ST926, ST31, and ST928, respectively, and three new STs were identified (ST925, ST926, and ST928).
CONCLUSION
This study provides genetic information by comparing genome sequences of several isolates from a community of various origins, with the aim of optimizing empirical antibiotic medication and contributing to worldwide efforts to tackle antibiotic resistance.
Topics: Humans; Stenotrophomonas maltophilia; Anti-Bacterial Agents; Anti-Infective Agents; Drug Resistance, Microbial; Genomics; Gram-Negative Bacterial Infections; Microbial Sensitivity Tests
PubMed: 38089814
DOI: 10.3389/fcimb.2023.1266295 -
International Journal of Microbiology 2023Today, () is a major opportunistic pathogen among hospitalized or immunocompromised patients. Antibiotic-resistant clinical isolates are increasing in several parts of...
OBJECTIVES
Today, () is a major opportunistic pathogen among hospitalized or immunocompromised patients. Antibiotic-resistant clinical isolates are increasing in several parts of the world. Various antibiotic-resistance and biofilm-forming genes are identified in this bacterium. Its capacity to form biofilms is an important virulence factor that may impact antibiotic-resistance patterns. In the current study, we evaluated the biofilm-formation capacity, antibiotic-resistance profile, and prevalence of biofilm-forming genes as well as antibiotic resistance genes among isolates.
MATERIALS AND METHODS
In this cross-sectional study, 94 clinical isolates were recovered from four tertiary-care hospitals in Iran between 2021 and 2022. The presence of the selected antibiotic-resistance genes and biofilm-forming genes was examined by polymerase chain reaction (PCR). The ability of biofilm formation was examined by microtiter plate assay. The Kirby-Bauer disc diffusion method was used to evaluate the trimethoprim-sulfamethoxazole (TMP-SMX), levofloxacin, and minocycline resistance.
RESULTS
is mainly isolated from bloodstream infections. Notably, 98.93% of isolates were biofilm producers, of which 19.35%, 60.22%, and 20.43% produced strong, moderate, and weak biofilm, respectively. The frequency of biofilm genes was 100%, 97.88%, 96.80%, and 75.53% for -1, and , respectively. Isolates with the genotype of -1+/+/+/+ were mostly strong biofilm producers. Among the antibiotic-resistance genes, the had the highest prevalence (76.59%, 72.34%, and 64.89), respectively. Antimicrobial susceptibility evaluation showed 1.06%, 3.19%, and 6.3% resistance to minocycline, TMP-SMX, and levofloxacin.
CONCLUSION
The results of the current study demonstrated that isolates differ in biofilm-forming ability. Moreover, -1, , and genes were presented in all strong biofilm producers. Although the overall resistance rate to the evaluated antibiotics was high, there was no statistically significant relation between antibiotic resistance and the type of biofilm.
PubMed: 37692920
DOI: 10.1155/2023/8873948 -
Applied and Environmental Microbiology Jun 2023Stenotrophomonas maltophilia is an environmental bacterium as well as an emerging opportunistic multidrug-resistant pathogen. They use the endogenous diffusible signal...
Stenotrophomonas maltophilia is an environmental bacterium as well as an emerging opportunistic multidrug-resistant pathogen. They use the endogenous diffusible signal factor (DSF) quorum sensing (QS) system to coordinate population behavior and regulate virulence processes but can also respond to exogenous N-acyl-homoserine lactone (AHL) signals produced by neighboring bacteria. The effect of these QS signals on the global gene expression of this species remains, however, unknown. Whole-transcriptome sequencing analyses were performed for exponential cultures of S. maltophilia K279a treated with exogenous DSF or AHLs. Addition of DSF and AHLs signals resulted in changes in expression of at least 2-fold for 28 and 82 genes, respectively. Interestingly, 22 of these genes were found upregulated by both QS signals, 14 of which were shown to also be induced during the stationary phase. Gene functions regulated by all conditions included lipid and amino acid metabolism, stress response and signal transduction, nitrogen and iron metabolism, and adaptation to microoxic conditions. Among the common top upregulated QS core genes, a putative TetR-like regulator (locus tag SMLT2053) was selected for functional characterization. This regulator controls its own β-oxidation operon (-), and it is found to sense long-chain fatty acids (FAs), including the QS signal DSF. Gene knockout experiments reveal that operon - is involved in biofilm formation. Overall, our findings provide clues on the effect that QS signals have in S. maltophilia QS-related phenotypes and the transition from the exponential to the stationary phase and bacterial fitness under high-density growth. The quorum sensing system in Stenotrophomonas maltophilia, in addition to coordinating the bacterial population, controls virulence-associated phenotypes, such as biofilm formation, motility, protease production, and antibiotic resistance mechanisms. Biofilm formation is frequently associated with the persistence and chronic nature of nosocomial infections. In addition, biofilms exhibit high resistance to antibiotics, making treatment of these infections extremely difficult. The importance of studying the metabolic and regulatory systems controlled by quorum sensing autoinducers will make it possible to discover new targets to control pathogenicity mechanisms in S. maltophilia.
Topics: Quorum Sensing; Stenotrophomonas maltophilia; Biofilms; Virulence; Acyl-Butyrolactones; Fatty Acids
PubMed: 37272812
DOI: 10.1128/aem.00635-23 -
Scientific Reports Dec 2023Prophages, which enables bacterial hosts to acquire novel traits, and increase genetic variation and evolutionary innovation, are considered to be one of the greatest...
Prophages, which enables bacterial hosts to acquire novel traits, and increase genetic variation and evolutionary innovation, are considered to be one of the greatest drivers of bacterial diversity and evolution. Stenotrophomonas maltophilia is widely distributed and one of the most important multidrug resistant bacteria in hospitals. However, the distribution and genetic diversity of S. maltophilia prophages have not been elucidated. In this study, putative prophages were predicted in S. maltophilia genomes by using virus prediction tools, and the genetic diversity and phylogeny of S. maltophilia and the prophages they harbor were further analyzed. A total of 356 prophage regions were predicted from 88 S. maltophilia genomes. Among them, 144 were intact prophages, but 77.09% of the intact prophages did not match any known phage sequences in the public database. The number of prophage carried by S. maltophilia is related to its host habitat and is an important factor affecting the size of the host genome, but it is not related to the genetic diversity of the prophage. The prediction of auxiliary genes encoded by prophage showed that antibiotic resistance genes was not predicted for any of the prophages except for one questionable prophage, while 53 virulence genes and 169 carbohydrate active enzymes were predicted from 11.24 and 44.1% prophages, respectively. Most of the prophages (72.29%) mediated horizontal gene transfer of S. maltophilia genome, but only involved in 6.25% of the horizontal gene transfer events. In addition, CRISPR prediction indicated 97.75% S. maltophilia strains contained the CRISPR-Cas system containing 818 spacer sequences. However, these spacer sequences did not match any known S. maltophilia phages, and only a few S. maltophilia prophages. Comparative genomic analysis revealed a highly conserved and syntenic organization with genomic rearrangement between the prophages and the known related S. maltophilia phages. Our results indicate a high prevalence and genetic diversity of prophages in the genome of S. maltophilia, as well as the presence of a large number of uncharacterized phages. It provides an important complement to understanding the diversity and biological characteristics of phages, as well as the interactions and evolution between bacteria and phages.
Topics: Prophages; Phylogeny; Stenotrophomonas maltophilia; Genomics; Gene Transfer, Horizontal
PubMed: 38135742
DOI: 10.1038/s41598-023-50449-x -
Frontiers in Cellular and Infection... 2024The hemin acquisition system is composed of an outer membrane TonB-dependent transporter that internalizes hemin into the periplasm, periplasmic hemin-binding proteins...
INTRODUCTION
The hemin acquisition system is composed of an outer membrane TonB-dependent transporter that internalizes hemin into the periplasm, periplasmic hemin-binding proteins to shuttle hemin, an inner membrane transporter that transports hemin into the cytoplasm, and cytoplasmic heme oxygenase to release iron. Fur and HemP are two known regulators involved in the regulation of hemin acquisition. The hemin acquisition system of is poorly understood, with the exception of HemA as a TonB-dependent transporter for hemin uptake.
METHODS
Putative candidates responsible for hemin acquisition were selected via a homolog search and a whole-genome survey of . Operon verification was performed by reverse transcription-polymerase chain reaction. The involvement of candidate genes in hemin acquisition was assessed using an in-frame deletion mutant construct and iron utilization assays. The transcript levels of candidate genes were determined using quantitative polymerase chain reaction.
RESULTS
and operons were selected as candidates for hemin acquisition. Compared with the parental strain, and mutants displayed a defect in their ability to use hemin as the sole iron source for growth. However, hemin utilization by the and mutants was comparable to that of the parental strain. expression was repressed by Fur in iron-replete conditions and derepressed in iron-depleted conditions. HemP negatively regulated expression. Like , was repressed by Fur in iron-replete conditions; however, was moderately derepressed in response to iron-depleted stress and fully derepressed when hemin was present. Unlike and , the operon was constitutively expressed, regardless of the iron level or the presence of hemin, and Fur and HemP had no influence on its expression.
CONCLUSION
HemA, HemU, and TonB1 contribute to hemin acquisition in . Fur represses the expression of and in iron-replete conditions. expression is regulated by low iron levels, and HemP acts as a negative regulator of this regulatory circuit. expression is regulated by low iron and hemin levels in a -dependent manner.
Topics: Hemin; Stenotrophomonas maltophilia; Bacterial Proteins; Membrane Proteins; Iron
PubMed: 38596648
DOI: 10.3389/fcimb.2024.1380976 -
Infection and Drug Resistance 2023To better guide clinical use, we determined the in vitro antimicrobial activity of the new drug eravacycline and other tetracycline derivatives against levofloxacin...
In vitro Antimicrobial Activity and Dose Optimization of Eravacycline and Other Tetracycline Derivatives Against Levofloxacin-Non-Susceptible and/or Trimethoprim-Sulfamethoxazole-Resistant .
PURPOSE
To better guide clinical use, we determined the in vitro antimicrobial activity of the new drug eravacycline and other tetracycline derivatives against levofloxacin (LVFX)-non-susceptible and/or trimethoprim-sulfamethoxazole (TMP-SMZ)-resistant and evaluated their dosing regimens.
METHODS
Seventy-seven unique strains of were isolated from sputa samples and airway aspirate samples that were either LVFX-non-susceptible and/or TMP-SMZ-resistant. Monte Carlo simulations were performed for different dosing regimens according to the population pharmacokinetic parameters of antibiotics in patients with respiratory tract infections at the minimum inhibitory concentration (MIC).
RESULTS
Eravacycline had excellent in vitro antibacterial activity against LVFX-non-susceptible and/or TMP-SMZ-resistant . Monte Carlo simulations showed that for LVFX-non-susceptible strains, the cumulative fraction of response (CFR) of minocycline at the conventional recommended dose of 100 mg q12 h was 90.90%; for TMP-SMZ-resistant strains, the CFR of minocycline at a high dose of 200 mg q12 h was only 91.64%. For strains resistant to both LVFX and TMP-SMZ, the CFR of minocycline at a high dose of 200 mg q12 h was 89.81%. In contrast, the CFR of tigecycline was less than 40%, even at a dose of 100 mg q12 h.
CONCLUSION
For pneumonia, minocycline is better for that is non-susceptible to LVFX; for TMP-SMZ-resistant strains and strains that are not susceptible to either LVFX or TMP-SMZ, the efficiency of eravacycline requires further evaluation. Eravacycline may be a better choice for extremely resistant strains that are non-susceptible to LVFX, TMP-SMZ, and minocycline.
PubMed: 37705512
DOI: 10.2147/IDR.S425061 -
Infection and Drug Resistance 2023, a multidrug-resistant pathogen can cause hospital-acquired infections such as pneumonia, or bloodstream infection. infection is associated with high mortality rates....
The Activities of Antimicrobials Against Isolates and Evaluation of Clinical Outcomes Among Treatment Regimens in Patients with Infections: A Retrospective Multicenter Cohort Study.
PURPOSE
, a multidrug-resistant pathogen can cause hospital-acquired infections such as pneumonia, or bloodstream infection. infection is associated with high mortality rates. This retrospective study examined the antimicrobial susceptibility profile of clinical isolates and evaluated clinical outcomes, treatment regimens, and risk factors associated with 30-day mortality or treatment failure of infections at three tertiary care hospitals in Central Thailand.
PATIENTS AND METHODS
The characteristics, microbiological data, and clinical treatment outcomes were derived from medical records obtained from three tertiary care hospitals in Central Thailand from January 2017 to October 2022. The primary outcomes were treatment failure and 30-day mortality. The antimicrobial susceptibility rates of trimethoprim-sulfamethoxazole (TMP-SMX), levofloxacin, and ceftazidime were determined by minimum inhibitory concentration (MIC), which were based on broth microdilution and clear zone diameters using the disk diffusion method. However, we also report the susceptibility of minocycline and tigecycline in some clinical strains (n = 149) and determined by MIC with E-test method.
RESULTS
The antimicrobial susceptibility rates to TMP-SMX, levofloxacin, and ceftazidime were 97.1%, 93%, and 55.3%, respectively. The treatment failure rate and 30-day mortality were 66.3% and 49%, respectively. Significant factors associated with treatment failure included APACHE II score ≥15 (OR 3.37, 95% confidence interval (CI) 1.46-7.76), polymicrobial infections (OR 3.20, 95% CI 1.35-7.55). The significant factors associated with reduced treatment failure was treatment with TMP-SMX-based regimen (OR 0.29, 95% CI 0.11-0.76). The 30-day mortality rate was associated with APACHE II score ≥15 (OR 3.27, 95% CI 1.45-7.39) and septic shock (OR 2.53, 95% CI 1.36-4.69).
CONCLUSION
The results indicate a high mortality rate for infection. The predictive factors for an unfavourable outcome were severity of illness, septic shock, and non-use of TMP-SMX. Therefore, a TMP-SMX-based regimen is recommended for the treatment of infections.
PubMed: 37581163
DOI: 10.2147/IDR.S416678