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Cell Metabolism Jan 2024The gut microbiome has been found to play a crucial role in the treatment of multiple myeloma (MM), which is still considered incurable due to drug resistance. In...
The gut microbiome has been found to play a crucial role in the treatment of multiple myeloma (MM), which is still considered incurable due to drug resistance. In previous studies, we demonstrated that intestinal nitrogen-recycling bacteria are enriched in patients with MM. However, their role in MM relapse remains unclear. This study highlights the specific enrichment of Citrobacter freundii (C. freundii) in patients with relapsed MM. Through fecal microbial transplantation experiments, we demonstrate that C. freundii plays a critical role in inducing drug resistance in MM by increasing levels of circulating ammonium. The ammonium enters MM cells through the transmembrane channel protein SLC12A2, promoting chromosomal instability and drug resistance by stabilizing the NEK2 protein. We show that furosemide sodium, a loop diuretic, downregulates SLC12A2, thereby inhibiting ammonium uptake by MM cells and improving progression-free survival and curative effect scores. These findings provide new therapeutic targets and strategies for the intervention of MM progression and drug resistance.
Topics: Humans; Bortezomib; Multiple Myeloma; Gastrointestinal Microbiome; Cell Line, Tumor; Membrane Proteins; NIMA-Related Kinases; Solute Carrier Family 12, Member 2
PubMed: 38113887
DOI: 10.1016/j.cmet.2023.11.019 -
Frontiers in Microbiology 2023Gut microbiota plays an important role in colorectal cancer (CRC) pathogenesis through microbes and their metabolites, while oral pathogens are the major components of...
OBJECTIVE
Gut microbiota plays an important role in colorectal cancer (CRC) pathogenesis through microbes and their metabolites, while oral pathogens are the major components of CRC-associated microbes. Multiple studies have identified gut and fecal microbiome-derived biomarkers for precursors lesions of CRC detection. However, few studies have used salivary samples to predict colorectal polyps. Therefore, in order to find new noninvasive colorectal polyp biomarkers, we searched into the differences in fecal and salivary microbiota between patients with colorectal polyps and healthy controls.
METHODS
In this case-control study, we collected salivary and fecal samples from 33 patients with colorectal polyps (CP) and 22 healthy controls (HC) between May 2021 and November 2022. All samples were sequenced using full-length 16S rRNA sequencing and compared with the Nucleotide Sequence Database. The salivary and fecal microbiota signature of colorectal polyps was established by alpha and beta diversity, Linear discriminant analysis Effect Size (LEfSe) and random forest model analysis. In addition, the possibility of microbiota in identifying colorectal polyps was assessed by Receiver Operating Characteristic Curve (ROC).
RESULTS
In comparison to the HC group, the CP group's microbial diversity increased in saliva and decreased in feces ( < 0.05), but there was no significantly difference in microbiota richness ( > 0.05). The principal coordinate analysis revealed significant differences in β-diversity of salivary and fecal microbiota between the CP and HC groups. Moreover, LEfSe analysis at the species level identified and as the major contributors to the salivary microbiota, and and to the fecal microbiota of patients with polyps. Salivary and fecal bacterial biomarkers showed Area Under ROC Curve of 0.8167 and 0.8051, respectively, which determined the potential of diagnostic markers in distinguishing patients with colorectal polyps from controls, and it increased to 0.8217 when salivary and fecal biomarkers were combined.
CONCLUSION
The composition and diversity of the salivary and fecal microbiota were significantly different in colorectal polyp patients compared to healthy controls, with an increased abundance of harmful bacteria and a decreased abundance of beneficial bacteria. A promising non-invasive tool for the detection of colorectal polyps can be provided by potential biomarkers based on the microbiota of the saliva and feces.
PubMed: 37655344
DOI: 10.3389/fmicb.2023.1182346 -
One Health (Amsterdam, Netherlands) Dec 2023The emergence of extended-spectrum β-lactamase and carbapenemase-producing Enterobacterales (ESBL-E and CPE, respectively) is a threat to modern medicine, as infections...
The emergence of extended-spectrum β-lactamase and carbapenemase-producing Enterobacterales (ESBL-E and CPE, respectively) is a threat to modern medicine, as infections become increasingly difficult to treat. These bacteria have been detected in aquatic environments, which raises concerns about the potential spread of antibiotic resistance through water. Therefore, we investigated the occurrence of ESBL-E and CPE in surface water in Lower Saxony, Germany, using phenotypic and genotypic methods. Water samples were collected from two rivers, five water canals near farms, and 18 swimming lakes. ESBL-E and CPE were isolated from these samples using filters and selective agars. All isolates were analyzed by whole genome sequencing. Multidrug-resistant Enterobacterales were detected in 4/25 (16%) water bodies, including 1/2 rivers, 2/5 water canals and 1/18 lakes. Among all samples, isolates belonging to five different species/species complexes were detected: ( = 10), complex ( = 4), ( = 3), ( = 2), and (n = 2) Of the 21 isolates, 13 (62%) were resistant at least to 3rd generation cephalosporins and eight (38%) additionally to carbapenems. CPE isolates harbored ( = 5), and ( = 2), or ( = 1); additionally, was detected in one isolate. Two out of eight CPE isolates were resistant to cefiderocol and two to colistin. Resistance to 3rd generation cephalosporins was mediated by ESBL ( = 10) or AmpC ( = 3). The presence of AmpC-producing Enterobacterales, ESBL-E and CPE in northern German surface water samples is alarming and highlights the importance of aquatic environments as a potential source of MDR bacteria.
PubMed: 37583366
DOI: 10.1016/j.onehlt.2023.100606 -
Annals of Medicine and Surgery (2012) Nov 2023Vaccination against coronavirus disease 2019 (COVID-19) is essential for controlling the ongoing cases of this disease. Citrobacter infections of the bones and joints...
INTRODUCTION
Vaccination against coronavirus disease 2019 (COVID-19) is essential for controlling the ongoing cases of this disease. Citrobacter infections of the bones and joints are extremely uncommon. Thromboembolism and deep vein thrombosis (DVT) are very rare complications.
CASE PRESENTATION
The authors present a rare case of osteomyelitis, septic arthritis, deep venous thrombosis, and pulmonary embolism in a 15-year-old previously healthy boy occurring shortly after receiving the second dose of the Moderna COVID-19 vaccine. He experienced pain, swelling in the right leg, shortness of breath, and fever, followed by chest pain and leg edema. Treatment included anticoagulation, ketorolac for pain management, antipyretics, and intravenous antibiotics (Tazobactam/Piperacillin, Linezolid, Clindamycin) for osteomyelitis.
DISCUSSION
The risk of COVID-19 vaccine-related thrombotic events is minimal. Thrombotic events reported among mRNA is very rare. bone and joint infections are very rare, accounting for a small percentage of cases. Some documented cases include cefotaxime-resistant strains causing necrotizing fascitis and osteomyelitis, including postarthroplasty infections. Due to the diverse range of susceptibility patterns and the widespread occurrence of drug resistance, personalized treatment based on culture and sensitivity testing is recommended. However, in rare cases, severe complications like DVT and joint infections associated with Citrobacter infection may occur and should be reported to the vaccine adverse events reporting system.
CONCLUSION
Administering the COVID-19 vaccine to enhance natural antibodies is crucial, despite the low risk of infection, thromboembolism, and DVT. Healthcare providers should stay vigilant about adverse effects postvaccination and promptly report those cases.
PubMed: 37915646
DOI: 10.1097/MS9.0000000000001351 -
Frontiers in Microbiology 2023To explore the genetic characteristics of the IMP-4, NDM-1, OXA-1, and KPC-2 co-producing multidrug-resistant (MDR) clinical isolate, wang9.
PURPOSE
To explore the genetic characteristics of the IMP-4, NDM-1, OXA-1, and KPC-2 co-producing multidrug-resistant (MDR) clinical isolate, wang9.
METHODS
MALDI-TOF MS was used for species identification. PCR and Sanger sequencing analysis were used to identify resistance genes. In addition to agar dilution, broth microdilution was used for antimicrobial susceptibility testing (AST). We performed whole genome sequencing (WGS) of the strains and analyzed the resulting data for drug resistance genes and plasmids. Phylogenetic trees were constructed with maximum likelihood, plotted using MAGA X, and decorated by iTOL.
RESULTS
carrying , , , and are resistant to most antibiotics, intermediate to tigecycline, and only sensitive to polymyxin B, amikacin, and fosfomycin. The coexists with the and the on a novel transferable plasmid variant pwang9-1, located on the integron In, transposon Tn, and integron In, respectively. The gene cassette sequence of integron In is , while the gene cassette sequence of In is The is located on the transposon Tn, and its sequence is ISISISIS The is located on the transposon Tn of plasmid pwang9-1, and its sequence is ISIS Phylogenetic analysis showed that most of the 34\u00B0 isolates from China were divided into three clusters. Among them, wang1 and wang9 belong to the same cluster as two strains of from environmental samples from Zhejiang.
CONCLUSION
We found carrying , , , and for the first time, and conducted in-depth research on its drug resistance mechanism, molecular transfer mechanism and epidemiology. In particular, we found that , , and coexisted on a new transferable hybrid plasmid that carried many drug resistance genes and insertion sequences. The plasmid may capture more resistance genes, raising our concern about the emergence of new resistance strains.
PubMed: 37378293
DOI: 10.3389/fmicb.2023.1074612 -
Antimicrobial Resistance and Infection... Jun 2023Accumulating evidence shows a role of the hospital wastewater system in the spread of multidrug-resistant organisms, such as carbapenemase producing Enterobacterales...
Sanitary installations and wastewater plumbing as reservoir for the long-term circulation and transmission of carbapenemase producing Citrobacter freundii clones in a hospital setting.
BACKGROUND
Accumulating evidence shows a role of the hospital wastewater system in the spread of multidrug-resistant organisms, such as carbapenemase producing Enterobacterales (CPE). Several sequential outbreaks of CPE on the geriatric ward of the Ghent University hospital have led to an outbreak investigation. Focusing on OXA-48 producing Citrobacter freundii, the most prevalent species, we aimed to track clonal relatedness using whole genome sequencing (WGS). By exploring transmission routes we wanted to improve understanding and (re)introduce targeted preventive measures.
METHODS
Environmental screening (toilet water, sink and shower drains) was performed between 2017 and 2021. A retrospective selection was made of 53 Citrobacter freundii screening isolates (30 patients and 23 environmental samples). DNA from frozen bacterial isolates was extracted and prepped for shotgun WGS. Core genome multilocus sequence typing was performed with an in-house developed scheme using 3,004 loci.
RESULTS
The CPE positivity rate of environmental screening samples was 19.0% (73/385). Highest percentages were found in the shower drain samples (38.2%) and the toilet water samples (25.0%). Sink drain samples showed least CPE positivity (3.3%). The WGS data revealed long-term co-existence of three patient sample derived C. freundii clusters. The biggest cluster (ST22) connects 12 patients and 8 environmental isolates taken between 2018 and 2021 spread across the ward. In an overlapping period, another cluster (ST170) links eight patients and four toilet water isolates connected to the same room. The third C. freundii cluster (ST421) connects two patients hospitalised in the same room but over a period of one and a half year. Additional sampling in 2022 revealed clonal isolates linked to the two largest clusters (ST22, ST170) in the wastewater collection pipes connecting the rooms.
CONCLUSIONS
Our findings suggest long-term circulation and transmission of carbapenemase producing C. freundii clones in hospital sanitary installations despite surveillance, daily cleaning and intermittent disinfection protocols. We propose a role for the wastewater drainage system in the spread within and between rooms and for the sanitary installations in the indirect transmission via bioaerosol plumes. To tackle this problem, a multidisciplinary approach is necessary including careful design and maintenance of the plumbing system.
Topics: Humans; Aged; Citrobacter freundii; Wastewater; Sanitary Engineering; Retrospective Studies; Hospitals; Clone Cells
PubMed: 37337245
DOI: 10.1186/s13756-023-01261-9 -
Journal of Global Antimicrobial... Sep 2023Carbapenems are among the few effective antibiotics against multidrug-resistant Enterobacteriaceae. This study aimed at characterizing the plasmid content and resistome...
OBJECTIVES
Carbapenems are among the few effective antibiotics against multidrug-resistant Enterobacteriaceae. This study aimed at characterizing the plasmid content and resistome of clinical carbapenem-resistant Enterobacteriaceae (CRE) recovered from 2016 to 2019 from hospitalized patients in Lebanon.
METHODS
Plasmid typing and whole-genome sequencing were used to study the genomic characteristics of 65 clinical CREs including 27 Escherichia coli, 24 Klebsiella pneumoniae, one Klebsiella quasipneumoniae, three Morganella morganii, three Citrobacter freundii, five Enterobacter hormaechei, and two Serratia marcescens.
RESULTS
bla (33.8%; n = 22) and bla-like genes were among the detected resistance determinants, with two isolates co-harbouring bla. Various bla variants, bla (16.9%; n = 11), bla (9.2%; n = 6), bla (9.2%; n = 6), and bla (4.6%; n = 3), different ESBLs, and AmpC β-lactamases were detected. Carbapenem resistance determinants were linked to a variety of incompatibility groups with IncFIB(K) (43.1%; n = 28) being the most prevalent, followed by IncFIA (40.0%), IncL (35.4%), IncX3 (32.3%), IncI1 (32.3%), and IncFIIK (29.2%).
CONCLUSIONS
We analysed the clonality and resistance determinants of 65 multidrug-resistant (MDR) Enterobacteriaceae recovered in the period from 2016 to 2019 from a large tertiary hospital in Lebanon. NDM variants, OXA-48, and OXA-181 were the most prevalent detected carbapenemases and were mostly linked to the dissemination of IncL, IncX3, and IncF. This study reinforces the need to track the spread and dominance of clinically relevant carbapenemase-encoding plasmids in healthcare settings.
Topics: Humans; Carbapenem-Resistant Enterobacteriaceae; Enterobacteriaceae; Escherichia coli; Anti-Bacterial Agents; Sequence Analysis
PubMed: 37437842
DOI: 10.1016/j.jgar.2023.07.004 -
Frontiers in Microbiology 2023The increase in clinical with dual carbapenemase has become a serious healthcare concern. It is essential to characterize the transferability and potential...
INTRODUCTION
The increase in clinical with dual carbapenemase has become a serious healthcare concern. It is essential to characterize the transferability and potential dissemination of - and -coharboring carbapenem-resistant (CRCF).
METHODS
Four - and -coharboring CRCF strains were collected from our surveillance of the prevalence of carbapenem-resistant . The isolates were assessed using species identification, antimicrobial susceptibility testing, conjugation assays, whole-genome sequencing, plasmid stability, and fitness costs. Clonality, genome, plasmidome, and phylogeny were analyzed to reveal potential dissemination.
RESULTS
Three ST523 - and -coharboring CRCF strains, collected from the same hospital within 1 month, exhibited high homology (both identity and coverage >99%), implying clonal dissemination and a small-scale outbreak. Moreover, the and genes were coharbored on an IncR plasmid, probably generated by a -harboring plasmid acquiring , in these three strains. Importantly, the IncR plasmid may form a transferable hybrid plasmid, mediated by IS via transposition, with another IncFII plasmid included in the same strain. Furthermore, the and of the fourth CRCF strain are located on two different non-transferable plasmids lacking complete transfer elements. Additionally, throughout the course of the 10-day continuous passage, the genetic surroundings of in four CRCF strains were gradually excised from their plasmids after the 8th day, whereas they maintained 100% retention for . Genome and plasmidome analyses revealed that - or -harboring were divergent, and these plasmids have high homology to plasmids of other .
CONCLUSION
Clonal dissemination of ST523 - and -coharboring CRCF strains was detected, and we first reported and concomitantly located on one plasmid, which could be transferred with mediation by IS via transposition. Continued surveillance should urgently be implemented.
PubMed: 37664119
DOI: 10.3389/fmicb.2023.1239538 -
Infection and Drug Resistance 2023This research aims to profile ten novel strains of carbapenem-resistant (CRE) co-carrying and .
PURPOSE
This research aims to profile ten novel strains of carbapenem-resistant (CRE) co-carrying and .
METHODS
Clinical CRE strains, along with corresponding medical records, were gathered. To ascertain the susceptibility of the strains to antibiotics, antimicrobial susceptibility tests were conducted. To validate the transferability and cost of fitness of plasmids, conjugation experiments and growth curves were employed. For determining the similarity between different strains, ERIC-PCR was utilised. Meanwhile, whole genome sequencing (WGS) was performed to characterise the features of plasmids and their evolutionary characteristics.
RESULTS
During the course of this research, ten clinical CRE strains co-carrying and were gathered. It was discovered that five out of these ten strains exhibited resistance to tigecycline. A closer examination of the mechanisms underlying tigecycline resistance revealed that 11, , and existed concurrently within a single strain (CF10). This strain, with a minimum inhibitory concentration (MIC) of 32 mg/L to tigecycline, was obtained from a sepsis patient. Furthermore, an investigation of genome evolution implied that CF10 belonged to a novel ST type 696, which lacked analogous strains. Aligning plasmids exposed that similar plasmids all had less than 70% coverage when compared to pCF10-tmexCD1, pCF10-KPC, and pCF10-NDM. It was also found that 11, , and were transferred by 5393, 5, and 6296, respectively.
CONCLUSION
This research presents the first report of coexistence of 11, , and in a carbapenem and tigecycline-resistant strain, CF10.
IMPORTANCE
Tigecycline is considered a "last resort" antibiotic for treating CRE infections. The ongoing evolution of resistance mechanisms to both carbapenem and tigecycline presents an alarming situation. Moreover, the repeated reporting of both these resistance mechanisms within a single strain poses a significant risk to public health. The research revealed that the genes 11, , and , which cause carbapenem and tigecycline-resistance in the same strain, were located on mobile elements, suggesting a potential for horizontal transmission to other Gram-negative bacteria. The emergence of such a multi-resistant strain within hospitals should raise significant concern due to the scarcity of effective antimicrobial treatments for these "superbugs".
PubMed: 37692469
DOI: 10.2147/IDR.S426148