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Microbiome Mar 2024The International Space Station (ISS) stands as a testament to human achievement in space exploration. Despite its highly controlled environment, characterised by...
Genomic, functional, and metabolic enhancements in multidrug-resistant Enterobacter bugandensis facilitating its persistence and succession in the International Space Station.
BACKGROUND
The International Space Station (ISS) stands as a testament to human achievement in space exploration. Despite its highly controlled environment, characterised by microgravity, increased CO levels, and elevated solar radiation, microorganisms occupy a unique niche. These microbial inhabitants play a significant role in influencing the health and well-being of astronauts on board. One microorganism of particular interest in our study is Enterobacter bugandensis, primarily found in clinical specimens including the human gastrointestinal tract, and also reported to possess pathogenic traits, leading to a plethora of infections.
RESULTS
Distinct from their Earth counterparts, ISS E. bugandensis strains have exhibited resistance mechanisms that categorise them within the ESKAPE pathogen group, a collection of pathogens recognised for their formidable resistance to antimicrobial treatments. During the 2-year Microbial Tracking 1 mission, 13 strains of multidrug-resistant E. bugandensis were isolated from various locations within the ISS. We have carried out a comprehensive study to understand the genomic intricacies of ISS-derived E. bugandensis in comparison to terrestrial strains, with a keen focus on those associated with clinical infections. We unravel the evolutionary trajectories of pivotal genes, especially those contributing to functional adaptations and potential antimicrobial resistance. A hypothesis central to our study was that the singular nature of the stresses of the space environment, distinct from any on Earth, could be driving these genomic adaptations. Extending our investigation, we meticulously mapped the prevalence and distribution of E. bugandensis across the ISS over time. This temporal analysis provided insights into the persistence, succession, and potential patterns of colonisation of E. bugandensis in space. Furthermore, by leveraging advanced analytical techniques, including metabolic modelling, we delved into the coexisting microbial communities alongside E. bugandensis in the ISS across multiple missions and spatial locations. This exploration revealed intricate microbial interactions, offering a window into the microbial ecosystem dynamics within the ISS.
CONCLUSIONS
Our comprehensive analysis illuminated not only the ways these interactions sculpt microbial diversity but also the factors that might contribute to the potential dominance and succession of E. bugandensis within the ISS environment. The implications of these findings are twofold. Firstly, they shed light on microbial behaviour, adaptation, and evolution in extreme, isolated environments. Secondly, they underscore the need for robust preventive measures, ensuring the health and safety of astronauts by mitigating risks associated with potential pathogenic threats. Video Abstract.
Topics: Humans; Anti-Infective Agents; Enterobacter; Genomics; Microbiota; Space Flight; Spacecraft
PubMed: 38521963
DOI: 10.1186/s40168-024-01777-1 -
Pediatric Research Apr 2024The mechanism underlying anorectal malformations (ARMs)-related VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, and renal and limb... (Review)
Review
The mechanism underlying anorectal malformations (ARMs)-related VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, and renal and limb abnormalities) remains unclear. Copy number variation (CNV) contributed to VACTERL pathogenicity. Here, we report a novel CNV in 8p23 and 12q23.1 identified in a case of ARMs-related VACTERL association. This 12-year-old girl presented a cloaca (urethra, vagina, and rectum opening together and sharing a single tube length), an isolated kidney, and a perpetuation of the left superior vena cava at birth. Her intelligence, growth, and development were slightly lower than those of normal children of the same age. Array comparative genomic hybridization revealed a 9.6-Mb deletion in 8p23.1-23.3 and a 0.52-Mb duplication in 12q23.1 in her genome. Furthermore, we reviewed the cases involving CNVs in patients with VACTERL, 8p23 deletion, and 12q23.1 duplication, and our case was the first displaying ARMs-related VACTERL association with CNV in 8p23 and 12q23.1. These findings enriched our understanding between VACTERL association and the mutations of 8p23 deletion and 12q23.1 duplication. IMPACT: This is a novel case of a Chinese girl with anorectal malformations (ARMs)-related VACTERL with an 8p23.1-23.3 deletion and 12q23.1 duplication. Cloaca malformation is presented with novel copy number variation in 8p23.1-23.3 deletion and 12q23.1 duplication.
Topics: Humans; Female; Limb Deformities, Congenital; Anal Canal; Child; Spine; Esophagus; DNA Copy Number Variations; Trachea; Heart Defects, Congenital; Chromosomes, Human, Pair 8; Chromosomes, Human, Pair 12; Genetic Association Studies; Mutation; Comparative Genomic Hybridization; Kidney; Cloaca; Phenotype; Abnormalities, Multiple
PubMed: 38135728
DOI: 10.1038/s41390-023-02928-0 -
Critical Reviews in Microbiology Feb 2024Healthy state is priority in today's world which can be achieved using effective medicines. But due to overuse and misuse of antibiotics, a menace of resistance has... (Review)
Review
Healthy state is priority in today's world which can be achieved using effective medicines. But due to overuse and misuse of antibiotics, a menace of resistance has increased in pathogenic microbes. World Health Organization (WHO) has announced ESKAPE pathogens (, spp.) as the top priority pathogens as these have developed resistance against certain antibiotics. To combat such a global issue, it is utmost important to identify novel therapeutic strategies/agents as an alternate to such antibiotics. To name certain antibiotic adjuvants including: inhibitors of beta-lactamase, efflux pumps and permeabilizers for outer membrane can potentially solve the antibiotic resistance problems. In this regard, inhibitors of lytic domain of lytic transglycosylases provide a novel way to not only act as an alternate to antibiotics but also capable of restoring the efficiency of previously resistant antibiotics. Further, use of bacteriophages is another promising strategy to deal with antibiotic resistant pathogens. Taking in consideration the alternatives of antibiotics, a green synthesis nanoparticle-based therapy exemplifies a good option to combat microbial resistance. As horizontal gene transfer (HGT) in bacteria facilitates the evolution of new resistance strains, therefore identifying the mechanism of resistance and development of inhibitors against it can be a novel approach to combat such problems. In our perspective, host-directed therapy (HDT) represents another promising strategy in combating antimicrobial resistance (AMR). This approach involves targeting specific factors within host cells that pathogens rely on for their survival, either through replication or persistence. As many new drugs are under clinical trials it is advisable that more clinical data and antimicrobial stewardship programs should be conducted to fully assess the clinical efficacy and safety of new therapeutic agents.
PubMed: 38381581
DOI: 10.1080/1040841X.2024.2313024 -
Folia Medica Cracoviensia Dec 2023The urachus is a tubular structure that is apparent on the third week and connects the ventral cloaca to the yolk sac, as a progression from the allantois. Following the...
The urachus is a tubular structure that is apparent on the third week and connects the ventral cloaca to the yolk sac, as a progression from the allantois. Following the normal regression procedure, the urachus remains as the median umbilical ligament. Urachal remnants are present in 1.03% of paediatric patients while in 92.5% of cases represent incidental findings. Urachal anomalies are classified in four types as patent urachus (50-52%), urachal sinus (15%), urachal cyst (30%) and urachal diverticulum (3-5%). Ultrasound scan is the most commonly performed diagnostic imaging study. In case of symptomatic urachal remnants, surgical excision is indicated. Asymptomatic urachal remnants that are diagnosed at the neonatal period or early infancy should be watched up to 6 months of age, as they are likely to resolve. In persistent or symptomatic urachal remnants there is a risk of inflammation or even malignancy development, therefore we believe that there is indication for preventive surgical excision that may be performed either open or laparoscopically or by robot-assisted laparoscopy.
Topics: Infant, Newborn; Humans; Child; Urachus; Urachal Cyst; Ultrasonography; Laparoscopy; Inflammation
PubMed: 38578347
DOI: 10.24425/fmc.2023.148760 -
Radiology May 2024A 76-year-old female patient with a history of rheumatoid arthritis, Sjögren syndrome, and hypertension presented with headache, fever, and dysphagia. The patient was...
A 76-year-old female patient with a history of rheumatoid arthritis, Sjögren syndrome, and hypertension presented with headache, fever, and dysphagia. The patient was taking prednisone and leflunomide to treat rheumatoid arthritis. The headache was primarily left sided and occasionally radiated to the occipital region. The patient had a high-grade fever spike, with a temperature of 104 °F (40 °C). Results of a prior lumbar puncture and temporal artery biopsy from an outside hospital were negative. Findings of a neurologic examination were unremarkable. Oropharyngeal examination for dysphagia revealed minimal pharyngeal motility, with pooling of food in the pharynx, which was thought to be due to cranial nerve dysfunction. Laboratory analysis revealed that, except for anemia, complete blood count parameters were within normal limits. C-reactive protein level (49.7 mg/L; reference range, 0.0-8.0 mg/L), erythrocyte sedimentation rate (>140 mm/h with Westergren method; reference range, 0-27 mm/h), and brain-type natriuretic peptide level (145 pg/mL; reference range, 0-100 pg/mL) were elevated. Blood and urine cultures were negative. A lumbar puncture was performed, which revealed cloudy cerebrospinal fluid (CSF), with an elevated CSF protein level (78 mg/dL; reference range, 7.0-35.0 mg/dL) and a low CSF glucose level (37 mg/dL [2.05 mmol/L]; reference range, 45-70 mg/dL [2.50-3.89 mmol/L]); otherwise, CSF encephalopathy, an autoimmune panel, and cultures were negative. CT and MRI of the brain with paranasal sinus were performed. Nasal endoscopy-guided drainage of the preclival fluid collection was performed, and biopsy of nasopharyngeal tissue was performed. Fluid culture revealed the growth of , as well as and . The patient received fluconazole, ceftriaxone, vancomycin, and metronidazole. Follow-up MRI was performed after 2 weeks.
Topics: Humans; Female; Aged; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Diagnosis, Differential
PubMed: 38805728
DOI: 10.1148/radiol.223335 -
Nature Communications Aug 2023Infections caused by metallo-beta-lactamase-producing organisms (MBLs) are a global health threat. Our understanding of transmission dynamics and how MBLs establish...
Infections caused by metallo-beta-lactamase-producing organisms (MBLs) are a global health threat. Our understanding of transmission dynamics and how MBLs establish endemicity remains limited. We analysed two decades of bla evolution in a hospital using sequence data from 270 clinical and environmental isolates (including 169 completed genomes) and identified the bla gene across 7 Gram-negative genera, 68 bacterial strains and 7 distinct plasmid types. We showed how an initial multi-species outbreak of conserved IncC plasmids (95 genomes across 37 strains) allowed endemicity to be established through the ability of bla to disseminate in successful strain-genetic setting pairs we termed propagators, in particular Serratia marcescens and Enterobacter hormaechei. From this reservoir, bla persisted through diversification of genetic settings that resulted from transfer of bla plasmids between bacterial hosts and of the integron carrying bla between plasmids. Our findings provide a framework for understanding endemicity and spread of MBLs and may have broader applicability to other carbapenemase-producing organisms.
Topics: Integrons; beta-Lactamases; Bacterial Proteins; Plasmids; Serratia marcescens; Carbapenems; Genomics; Microbial Sensitivity Tests; Anti-Bacterial Agents
PubMed: 37553339
DOI: 10.1038/s41467-023-39915-2 -
Antimicrobial Agents and Chemotherapy Dec 2023Carbapenems are considered last-resort antibiotics for the treatment of infections caused by multidrug-resistant , but carbapenem resistance due to acquisition of...
Carbapenems are considered last-resort antibiotics for the treatment of infections caused by multidrug-resistant , but carbapenem resistance due to acquisition of carbapenemase genes is a growing threat that has been reported worldwide. carbapenemase () is the most common type of carbapenemase in Canada and elsewhere; it can hydrolyze penicillins, cephalosporins, aztreonam, and carbapenems and is frequently found on mobile plasmids in the Tn transposon. This means that alongside clonal expansion, can disseminate through plasmid- and transposon-mediated horizontal gene transfer. We applied whole genome sequencing to characterize the molecular epidemiology of 829 carbapenemase-producing isolates collected by the Canadian Nosocomial Infection Surveillance Program from 2010 to 2021. Using a combination of short-read and long-read sequencing, we obtained 202 complete and circular -encoding plasmids. Using MOB-suite, 10 major plasmid clusters were identified from this data set which represented 87% (175/202) of the Canadian -encoding plasmids. We further estimated the genomic location of incomplete -encoding contigs and predicted a plasmid cluster for 95% (603/635) of these. We identified different patterns of carbapenemase mobilization across Canada related to different plasmid clusters, including clonal transmission of IncF-type plasmids (108/829, 13%) in clonal complex 258 and novel repE(pEh60-7) plasmids (44/829, 5%) in ST316, and horizontal transmission of IncL/M (142/829, 17%) and IncN-type plasmids (149/829, 18%) across multiple genera. Our findings highlight the diversity of genomic loci and indicate that multiple, distinct plasmid clusters have contributed to spread and persistence in Canada.
Topics: Humans; Canada; beta-Lactamases; Plasmids; Bacterial Proteins; Klebsiella pneumoniae; Anti-Bacterial Agents; Carbapenems; Genomics; Klebsiella Infections; Microbial Sensitivity Tests
PubMed: 37971242
DOI: 10.1128/aac.00860-23 -
Nature Communications Mar 2024Hospital surfaces can harbour bacterial pathogens, which may disseminate and cause nosocomial infections, contributing towards mortality in low- and middle-income...
Hospital surfaces can harbour bacterial pathogens, which may disseminate and cause nosocomial infections, contributing towards mortality in low- and middle-income countries (LMICs). During the BARNARDS study, hospital surfaces from neonatal wards were sampled to assess the degree of environmental surface and patient care equipment colonisation by Gram-negative bacteria (GNB) carrying antibiotic resistance genes (ARGs). Here, we perform PCR screening for extended-spectrum β-lactamases (bla) and carbapenemases (bla, bla-like and bla), MALDI-TOF MS identification of GNB carrying ARGs, and further analysis by whole genome sequencing of bacterial isolates. We determine presence of consistently dominant clones and their relatedness to strains causing neonatal sepsis. Higher prevalence of carbapenemases is observed in Pakistan, Bangladesh, and Ethiopia, compared to other countries, and are mostly found in surfaces near the sink drain. Klebsiella pneumoniae, Enterobacter hormaechei, Acinetobacter baumannii, Serratia marcescens and Leclercia adecarboxylata are dominant; ST15 K. pneumoniae is identified from the same ward on multiple occasions suggesting clonal persistence within the same environment, and is found to be identical to isolates causing neonatal sepsis in Pakistan over similar time periods. Our data suggests persistence of dominant clones across multiple time points, highlighting the need for assessment of Infection Prevention and Control guidelines.
Topics: Infant, Newborn; Humans; Developing Countries; Neonatal Sepsis; beta-Lactamases; Bacterial Proteins; Hospitals; Anti-Bacterial Agents; Klebsiella pneumoniae; Gram-Negative Bacteria; Microbial Sensitivity Tests
PubMed: 38553439
DOI: 10.1038/s41467-024-46684-z -
Environmental Monitoring and Assessment Aug 2023Lead (Pb) is a non-essential metal with high toxicity, is persistent, is not biodegradable, and has no known biological function. It is responsible for severe health and...
Lead (Pb) is a non-essential metal with high toxicity, is persistent, is not biodegradable, and has no known biological function. It is responsible for severe health and environmental issues that need appropriate remediation. Therefore, microbes have thrived in a lead-contaminated environment without exhibiting any negative impacts. The present study aimed to examine the toxic effects of lead on animals and the isolation, identification, and characterization of lead-resistant bacterial strains and their biodegradation potential. After oral administration of lead for 4 weeks, mice showed an elevated level of leukocytes and a decrease in TEC, Hb, PCV, MCV, MCH, and MCHC levels. However, a decline in body weight and inflammation and oxidative stress was observed in liver tissues. To remediate toxic heavy metal, lead-resistant bacterial strains were isolated, among which Enterobacter exhibited maximum degradation potential at high lead concentrations. It was identified by molecular basis and after 16S rRNA sequencing, and 99% resemblance was observed with Enterobacter cloacae. FT-IR analysis of the bacteria illustrated the presence of functional groups, including hydroxyl, carboxyl group, sulfide, and amino groups, on the bacterial cell surface involved in the adsorption of lead. Moreover, electron microscopy (SEM) revealed the morphological and physiochemical changes in the bacterial cell after biosorption, indicating the interaction of Cu ions with functional groups. To summarize, the findings show the highly toxic effects of lead on animals and humans and its effective biodegradation by the bacterial strains in the lead-contaminated environment. This biological strategy can be an ideal alternative to remediate heavy metals from contaminated sites to clean up the environment.
Topics: Humans; Animals; Mice; Lead; Biodegradation, Environmental; RNA, Ribosomal, 16S; Spectroscopy, Fourier Transform Infrared; Environmental Monitoring; Metals, Heavy
PubMed: 37589892
DOI: 10.1007/s10661-023-11632-9 -
Journal of Pediatric Urology Aug 2023Persistent cloaca, defined as confluence of the rectum, the vagina and the urethra into a single common channel, has an estimated incidence of 1/50,000 live births. We...
INTRODUCTION
Persistent cloaca, defined as confluence of the rectum, the vagina and the urethra into a single common channel, has an estimated incidence of 1/50,000 live births. We describe the buccal mucosa graft vaginoplasty for a 11 year old female with cloaca, who underwent at the age of 11 months a Peña repair. We performed the vaginoplasty after the onset of uterine pain due to the beginning of menstruation.
MATERIAL AND METHODS
We accessed the lower lip for superficial dissection to harvest the graft. The donor site has been kept with as much submucosal fat as possible to avoid damage to the buccinatoria muscles. A second graft was further obtained from the cheek. Both grafts were submitted to multiple small sections to produce a mesh graft and increase its size. A arciform incision anterior to the anal canal and posterior to the urethra was performed followed by consecutive dissection with eletrocautery to gain profundity. The mesh-graft was placed over the neovaginal cavity and sutured with 4.0 PDS monofilament suture used to suture and then quilt the graft in place. The vaginal capacity was confirmed by ease of a two-digit insertion. Haemostasis was confirmed before the insertion of a soft vaginal mold. The patient remained with an indwelling urinary catheter. The mold was equivalent to 24Fr and had 13 cm of profundity and Foley tube were removed after 14 days postoperatively.
RESULTS
Patient had an excellent postoperative course and had been instructed to perform vaginal dilatation every 3 h during the day. Current follow up is 10 months.
DISCUSSION
Buccal mucosal grafting has advantages over the use of keratinized skin flaps and intestinal flaps. Buccal mucosa is ideal for female genital reconstruction, given its color, texture, lack of hair and mild mucous production. In our particular case, we connected the neovagina after two months of adequate healing to the native 1⁄3 through laparoscopic approach.
CONCLUSIONS
BMG vaginoplasty is a viable alternative to treat females with cloaca at adolescence.
Topics: Adolescent; Humans; Female; Infant; Child; Mouth Mucosa; Plastic Surgery Procedures; Vagina; Surgical Flaps; Rectum
PubMed: 37120365
DOI: 10.1016/j.jpurol.2023.03.036