Distribution diversity and expression regulation of class 1 integron promoters in clinical isolates of Morganella morganii.

Background: Morganella morganii is an emerging nosocomial opportunistic pathogen with increasing multidrug resistance. Antibiotic resistance, driven primarily by the horizontal transfer of resistance genes, has become a global health crisis. Integrons, mobile genetic elements, are now understood to facilitate the transfer of these genes, contributing to the rapid proliferation of resistant strains. Understanding the regulatory role of integrons in drug resistance gene expression is crucial for developing novel strategies to combat this pressing public health issue. Objective: To investigate the distribution of promoter types in the variable regions of class 1 integrons isolated from clinical isolates of M. morganii and their regulatory role in the expression of downstream drug resistance gene cassettes. Methods: Ninety seven clinical isolates of M. morganii were screened for the presence of class 1 integrons (intI1) using polymerase chain reaction (PCR). Gene cassettes within the variable regions of positive isolates were characterized, and the gene cassette promoter Pc variants and downstream auxiliary promoter P2 were identified. Enterobacterial repetitive intergenic consensus (ERIC)-PCR was employed for homology analysis. Recombinant plasmids containing different variable region promoters and gene cassettes were constructed to evaluate drug resistance genes and integrase (intI1) expression levels using reverse transcription-quantitative PCR (RT-qPCR) and antimicrobial susceptibility testing. Results: Of the clinical isolates, 28.9% (n = 28/97) were positive for class 1 integrons. 24.7% (n = 24/97) of these isolates carried gene cassettes encoding resistance to aminoglycosides and trimethoprim. Three Pc promoter types (PcH1, PcS, and PcW) were identified, while all P2 promoters were inactive with a 14-base pair spacing between the -35 and -10 regions. ERIC-PCR analysis classified the integron-positive strains into 6 genotypes, with high consistency in promoter types and gene cassettes within each genotype. RT-qPCR and antimicrobial susceptibility testing demonstrated that strong promoters significantly enhanced the expression of downstream drug resistance gene cassettes compared to weak promoters. Additionally, RT-qPCR revealed a negative correlation between intI1 expression and Pc promoter strength. Conclusion: Class 1 integrons are prevalent in M. morganii. The promoter types within these integrons are diverse, and promoter strength is closely linked to downstream gene cassette expression. Integron-positive strains exhibit high homology, suggesting horizontal gene transfer and dissemination in clinical settings.

Identification and characterization of Morganella morganii strain YC12-C3 and Enterococcus faecalis strain YC12-C10 and elucidation of its deoxynivalenol-degrading potential.

Deoxynivalenol ( DON) is one of the most harmful mycotoxins in food or feed or Traditional Chinese Medicine. An efficient and applicable method for the detoxification of DON is urgently developed. 1152 strains were isolated from the intestinal contents of crucian. Morganella morganii YC12-C3 and Enterococcus faecalis YC12-C10 were screened with the highest degradation rate of DON via HPLC methods. The optimal degradation condition of YC12-C3 and YC12-C10 is co-cultured 24 h and 36 h at 28 ℃ in LB medium with pH 7 and 1.0% inoculation dosage, respectively. LC-MS/MS and 1H NMR results show that YC12-C10 and YC12-C3 can transform DON to 3-deoxy-6-demethanol-DON, a new metabolite biotransformed from DON, by deoxidization at C3 hydroxy and de-methanal reaction at methanol moiety of C6. In addition, the DON-degradation in agricultural material assay showed that YC12-C10 and YC12-C3 can degrade 150 µg·kg-1 DON in Coix lacryma-jobi, with a degradation rate of 68.89% and 59.94%, respectively. This result shows that YC12-C10 and YC12-C3 have a sound efficiency in removing DON ability in Coix lacryma-jobi, providing a new strain resource and application technique for biological detoxification of DON in food or feed or TCM industry.

Treatment of Morganella morganii-Associated Non-healing Diabetic Foot Ulcer With Vaporous Hyperoxia Therapy: A Case Report.

Diabetic foot ulcers represent a significant complication of diabetes mellitus, characterized by mechanical changes of bony architecture often leading to chronic wounds with increased risk of infection and impaired healing. Morganella morganii, a Gram-negative bacterium, is one of the pathogens found in infected diabetic foot ulcers. It is a human gastrointestinal commensal organism that may cause widespread deadly infections. This report discusses the case of a 76-year-old male with diabetes mellitus who presented with M. morganii diabetic foot ulcer to an in-patient rehabilitation facility. Despite conventional wound care and antibiotic therapy, the ulcer failed to improve. The management approach for this patient consisted of a rehabilitation modality called Vaporox, a machine that utilizes vaporous hyperoxia therapy (VHT), as it combines ultrasonic mist and high concentration of oxygen to fasten revascularization and healing. This case highlights the potential efficacy of VHT as an adjunctive therapy for the management of diabetic foot ulcers, particularly those complicated by pathogens, such as M. morganii.

Tracing the possible evolutionary trends of Morganella morganii: insights from molecular epidemiology and phylogenetic analysis.

Morganella morganii, encompassing two subspecies, subsp. morganii and subsp. sibonii, is a common opportunistic pathogen, notable for intrinsic resistance to multiple antimicrobial agents. Despite its clinical significance, research into the potential evolutionary dynamics of M. morganii remains limited. This study involved the analysis of genome sequences from 431 M. morganii isolates, comprising 206 isolates that cause host infections, obtained from this study and 225 from the NCBI genome data sets. A diverse array of antimicrobial resistance genes (ARGs) was identified in M. morganii isolates, including mcr-1, tet(X4), tmexCD-toprJ, and various carbapenemase genes. In addition, a novel blaKPC-2-bearing plasmid with demonstrated conjugative capability was discovered in M. morganii. The majority of virulence-related genes (VRGs), except for the hlyCABD gene cluster, were found in almost all M. morganii. Three novel genospecies of M. morganii were identified, designated as M. chanii, M. variant1, and M. variant2. Compared to M. sibonii, M. chanii genospecies possessed a greater number of flagellar-related genes, typically located within mobile genetic elements (MGEs), suggesting potential for better environmental adaptability. Phylogenetic analysis further disclosed that M. morganii was divided into 12 sequence clusters (SCs). Particularly, SC9 harbored an elevated abundance of ARGs and VRGs, mainly toxin-related genes, and was associated with a higher presence of MGEs compared to non-SC9 strains. The collective findings suggest that M. morganii undergoes evolution driven by the influence of MGEs, thereby significantly enhancing its adaptability to selective pressures of environmental changes and clinical antimicrobial agents.IMPORTANCEThe growing clinical significance of Morganella morganii arises from its abundant virulence factors and antimicrobial resistance genes, resulting in elevated infection rates and increased clinical scrutiny. However, research on the molecular epidemiology and evolutionary trends of M. morganii has been scarce. Our study established a list of virulence-related genes (VRGs) for M. morganii and conducted a large-scale epidemiological investigation into these VRGs. Based on genomic classification, three novel genotypes of M. morganii were identified, representing evolutionary adaptations and responses to environmental challenges. Furthermore, we discovered the emergence of a sequence cluster enriched with antimicrobial resistance genes, VRGs, and mobile genetic elements, attributed to the selective pressure of antimicrobial agents. In addition, we identified a novel conjugative plasmid harboring the blaKPC-2 gene. These findings hold significance in monitoring and comprehending the epidemiology of M. morganii.

Isolation and Identification of Morganella morganii from Rhesus Monkey (Macaca mulatta) in China.

A bacterium was isolated and identified from the secretion of a rhesus monkey with endometritis. The morphological results showed that the strain exhibited round, convex, gray-white colonies with smooth surfaces and diameters ranging from 1 to 2 mm when cultured on Columbia blood agar at 37 °C for 24 h; on salmonella-shigella agar (S.S.) at 37 °C for 24 h, the colonies appeared round, flat, and translucent. Gram staining showed negative results with blunt ends and non-spore-forming characteristics. Molecular biology results showed that the 16S rRNA sequence of the strain revealed over 96.9% similarity with published sequences of M. morganii from different sources in the NCBI GenBank database. Morphological and molecular biology analysis confirmed that the strain (RM2023) isolated from cervical secretions of rhesus monkey was M. morganii. Drug sensitivity testing demonstrated that the isolated strain (RM2023) was sensitive to ceftriaxone, amikacin, gentamicin, cefazolin, cefuroxime, ceftazidime, levofloxacin, cotrimoxazole, norfloxacin, and tetracycline; moderately sensitive to ampicillin; and resistant to penicillin, vancomycin, ciprofloxacin, and clindamycin. The research findings provide valuable insights for disease prevention in rhesus monkeys and contribute to molecular epidemiological studies.

A novel method for enrichment of Morganella morganii in fecal samples using designed culture medium.

Morganella morganii is a gram negative, facultative anaerobic rod-shaped bacterium, commonly found in environment and in the intestine of human, mammals, and reptiles as a part of their gut microbiome. M. morganii can cause Gram-negative folliculitis, black nail infection, acute retiform purpura, fetal demise, and subdural empyema. The increasing frequency of M. morganii infections generate the need for efficient methods to enrich the presence of M. morganii in clinical samples to make its detection easier. Culturomics aims to grow and maximize the number of culturable bacteria. Different methods are followed to maximize the growth of minority population of bacteria by disrupting the growth of bacteria which are present in higher concentration. This article presents a method for selective enriching the M. morganii in human fecal samples. This method includes prior incubation of fecal microbiota in an anaerobic environment, adding supplement like fecal water to give dormant bacteria a break to become active to grow to threshold concentration, and an enrichment stage which provides the additional opportunity of growing to M. morganii on the selective medium. This method also provides an ingenuous way for augmenting the growth of fecal M. morganii species.

Pectoralis Major Pyomyositis in a Patient With Diabetes: A Case Report and Literature Review.

Pyogenic myositis is a bacterial infection of skeletal muscle that is usually caused by Staphylococcus aureus and is common in tropical regions. Recently, this infection has also been reported in immunocompromised patients in temperate regions. The lower extremities and trunk are most affected, while involvement of the chest wall is rare. We report a case of pectoralis major pyomyositis caused by Morganella morganii in an 82-year-old Japanese man with type 2 diabetes mellitus who had undergone stenting for myocardial infarction. Four months prior to visiting our hospital, the patient became aware of pain in the right chest area, which gradually became swollen. One month before the visit, the pain and swelling had become more severe. At the visit, there was swelling in the right anterior thoracic region with a diameter of 10 cm and pain in the same region. On physical examination, his blood pressure was 133/64 mmHg, heart rate was 83 beats/min, and body temperature was 36.9℃. Initially, a sarcoma or other neoplastic lesion was suspected and a needle biopsy was performed. Pus was drained from the puncture site to collect wound culture. Needle biopsy of the lesion did not reveal any fungi or acid-fast bacteria, and a T-SPOT.TB test was negative. Computed tomography and magnetic resonance imaging suggested abscess formation under the pectoralis major muscle. A wound culture test detected Morganella morganii, and pectoralis major pyomyositis was diagnosed. Debridement was performed under general anesthesia. The necrotic pectoralis major muscle was excised, the abscess cavity was opened, and wound irrigation was performed. The postoperative course was good and the patient was discharged on the 16th postoperative day. There has been no recurrence in eight months postoperatively. Pectoralis major pyomyositis may not be relieved by antibiotics alone and may extend to deeper organs to form intrapleural abscesses. Therefore, prompt drainage should be performed to prevent serious complications in a case in which abscess formation is observed.

Brain abscess caused by Morganella morganii: A case report and review of the literature.

Background: Morganella morganii is a Gram-negative enteric rod found in the intestinal tracts of humans, mammals, and reptiles as normal flora. It is highly implicated in urinary tract infections, wound infections, and septicemia. The cerebral nervous system, especially brain abscess attributed to M. morganii, remains extremely rare. To the best of the author's knowledge, only eight documented cerebral brain abscesses caused by M. morganii have been reported in the literature. Case Description: A 48-year-old man presented with headache, fever, and irritability two months after endoscopic endonasal repair of the cranial base defect. Following imaging studies, a large left frontal abscess was found. The patient underwent a fine-needle aspiration through a burr hole following antimicrobial therapy. Conclusion: We report this case to create awareness among neurosurgeons and microbiologists that M. morganii, even though uncommon, is a cause of cerebral brain abscess. Prompt surgical management and appropriate antimicrobial therapy is the treatment of choice.

Draft genome sequences of four Morganella morganii strains isolated from Colombian colorectal cancer patient stool specimens.

We report the draft genome sequences of four Morganella morganii strains isolated from the stools of four patients diagnosed with colorectal cancer (CRC) in Medellín, Colombia. These genomes represent an important addition to the limited number of genomes of M. morganii strains originating from CRC patients currently available.

Epidemiology and clinical characteristics of Morganella morganii infections: A multicenter retrospective study.

BACKGROUND: Morganella morganii is a Gram-negative, opportunistic pathogen that can cause a variety of infections, including bloodstream infections, especially in those with compromised immune systems. It is often resistant to antibiotics, making it a difficult organism to treat. Limited studies have addressed M. morganii, but the organism is becoming increasingly recognized as a public health threat. More research is needed to understand the epidemiology and virulence factors of M. morganii in Saudi Arabia, as well as to develop effective treatment strategies. METHODS: This retrospective study included all M. morganii bloodstream infections patients admitted to five tertiary care hospitals in Saudi Arabia between 2015 and 2022. RESULTS: The study population included 75 patients (45 males and 30 females) between the age of 53-72 with a 54% ICU admission rate. The most comorbidities were hypertension followed by diabetes. The most common symptoms were fever, cough, shortness of breath, vomiting, and fatigue. The study also found that M. morganii was often resistant to multiple antibiotics, including ciprofloxacin, trimethoprim/sulfamethoxazole, gentamicin, amoxicillin, nitrofurantoin, and colistin. The most common treatment for M. morganii bacteremia was carbapenems, followed by aminoglycosides, ciprofloxacin, and colistin. Source control measures, such as surgery, line removal, drainage, and tissue removal, were also used in some cases. The study found that the in-hospital mortality rate for M. morganii bacteremia was 41%. The risk of mortality was increased in patients who were admitted to the ICU, who were older than 65 years, and who had Klebsiella pneumoniae co-infection. CONCLUSION: M. morganii bacteremia is a serious infection that is often resistant to antibiotics. Elderly patients and patients with comorbidities are at increased risk of mortality. Source control measures and appropriate antibiotic therapy are important for improving outcomes.

Clonal relationship, virulence genes, and antimicrobial resistance of Morganella morganii isolated from community-acquired infections and hospitalized patients: a neglected opportunistic pathogen.

Morganella morganii is a bacterium belonging to the normal intestinal microbiota and the environment; however, in immunocompromised individuals, this bacterium can become an opportunistic pathogen, causing a series of diseases, both in hospitals and in the community, being urinary tract infections more prevalent. Therefore, the objective of this study was to evaluate the prevalence, virulence profile, and resistance to antimicrobials and the clonal relationship of isolates of urinary tract infections (UTI) caused by M. morganii, both in the hospital environment and in the community of the municipality of Londrina-PR, in southern Brazil, in order to better understand the mechanisms for the establishment of the disease caused by this bacterium. Our study showed that M. morganii presents a variety of virulence factors in the studied isolates. Hospital strains showed a higher prevalence for the virulence genes zapA, iutA, and fimH, while community strains showed a higher prevalence for the ireA and iutA genes. Hospital isolates showed greater resistance compared to community isolates, as well as a higher prevalence of multidrug-resistant (MDR) and extended-spectrum beta lactamase (ESBL)-producing isolates. Several M. morganii isolates from both sources showed high genetic similarity. The most prevalent plasmid incompatibility groups detected were FIB and I1, regardless of the isolation source. Thus, M. morganii isolates can accumulate virulence factors and antimicrobial resistance, making them a neglected opportunistic pathogen.

Draft genome sequence data of heavy metal-resistant Morganella morganii WA01/MUTU, a silver nanoparticle (AgNP) synthesising bacterium.

Morganella morganii WA01/MUTU is a heavy metal tolerant strain capable of producing silver nanoparticles (AgNPs) from AgNO3. Here we present the draft genome sequence of M. morganii WA01/MUTU isolated from a water sample collected in Nakhon Pathom province, Thailand. The draft genome was sequenced on the Illumina NextSeq 550 sequencer. The genome consisted of 34 contigs with a total size of 3,991,804 bp, an N50 value of 364,423 bp and a GC content of 50.93%. The digital DNA-DNA hybridisation (dDDH) between WA01/MUTU and Morganella morganii (NBRC 3848) was 83.9%, identifying the strain as Morganella morganii. The data presented here can be used in comparative genomics to identify gene clusters involved in AgNP biosynthesis and secondary metabolite production. The draft genome sequence data was deposited at NCBI under Bioproject accession number PRJNA493966.

Morganella morganii and Enterococcus faecalis endophthalmitis following intravitreal injection.

BACKGROUND: Endophthalmitis following intravitreal injection is a potentially devastating complication of anti-VEGF injections. Post-injection endophthalmitis due to Enterococcus faecalis is rare, and no previous case of Morganella morganii endophthalmitis after intravitreal injection has been reported. CASE PRESENTATION: We present the first reported case of Morganella morganii and Enterococcus faecalis endophthalmitis after intravitreal injection in an immunocompetent patient in the absence of recent ocular surgery. Our patient presented with hand movement visual acuity one day after anti-VEGF injection and demonstrated no clinical improvement despite repeated intravitreal ceftazidime and vancomycin injections. A decision was made to proceed with early vitrectomy given failure of intravitreal antibiotics. Visual acuity improved to 6/90 at 12 weeks after vitrectomy without any evidence of disease recurrence. CONCLUSIONS: Post-injection endophthalmitis due to concurrent Morganella morganii and Enterococcus faecalis infections can have visually devastating consequences despite repeated empirical and targeted intravitreal antibiotics. Lack of clinical improvement following intravitreal antibiotics should warrant consideration of early vitrectomy. Our experience is a pertinent reminder of the ever-growing threat of uncommon and multi-resistant bacteria that must be considered when treating infections such as post-injection endophthalmitis.

Inhibition Mechanism of Lactiplantibacillus plantarum on the Growth and Biogenic Amine Production in Morganella morganii.

Morganella morganii, a spoilage bacterium in fermented foods, produces harmful biogenic amines (BAs). Although Lactiplantibacillus plantarum is widely used to inhibit spoilage bacteria, the inhibition pattern and inhibition mechanism of M. morganii by Lpb. plantarum are not well studied. In this study, we analysed the effects of the addition of Lpb. plantarum cell-free supernatant (CFS) on the growth and BA accumulation of M. morganii and revealed the mechanisms of changes in different BAs by using RNA sequencing transcriptome analysis. The results showed that Lpb. plantarum CFS could significantly inhibit M. morganii BAs in a weak acid environment (pH 6), and the main changes were related to metabolism. Carbohydrate and energy metabolism were significantly down-regulated, indicating that Lpb. plantarum CFS inhibited the growth activity and decreased the BA content of M. morganii. In addition, the change in histamine content is also related to the metabolism of its precursor amino acids, the change in putrescine content may also be related to the decrease in precursor amino acid synthesis and amino acid transporter, and the decrease in cadaverine content may also be related to the decrease in the cadaverine transporter. The results of this study help to inhibit the accumulation of harmful metabolites in fermented foods.

Morganella morganii: A Rare Cause of Early-Onset Neonatal Sepsis.

Morganella morganii is an opportunistic Gram-negative bacillus commonly found in the human gastrointestinal tract and the environment. In adults, it is often associated with nosocomial infections, primarily surgical wound infections, urinary tract infections, and hepatobiliary infections. It is a rare cause of early-onset neonatal sepsis, with fewer than 15 reported cases in the literature. The authors aim to present a case of a low birth weight preterm born at 28 weeks' gestation, who developed early-onset neonatal sepsis due to M. morganii. We successfully treated the infection using a combination of third-generation cephalosporin and aminoglycoside, and in this report, we explain the rationale behind employing this antibiotic therapy.

Isoniazid Mono-Resistant Tuberculosis Presenting as Empyema Thoracis With Citrobacter koseri and Morganella morganii Infections: The World's First Reported Case of Its Type.

Drug resistance is very common in developing countries. Isolated cases of concomitant infection with Mycobacterium tuberculosis, Citrobacter koseri, and Morganella morganii are rare. Furthermore, there is no report available in the literature of concurrent infection of Citrobacter koseri and Morganella morganii in an isoniazid mono-resistant tuberculosis patient. In this case, we present a concomitant infection with drug-resistant strains of Mycobacterium tuberculosis, Citrobacter koseri, and Morganella morganii in a 40-year-old Indian male who presented with fever, dry cough, and chest pain. He was initiated on an isoniazid mono regimen and a broad-spectrum antibiotic, following the national guidelines.

Probable Three-Species In Vivo Transfer of blaNDM-1 in a Single Patient in Greece: Occurrence of NDM-1-Producing Klebsiella pneumoniae, Proteus mirabilis, and Morganella morganii.

NDM carbapenemase-encoding genes disseminate commonly among Enterobacterales through transferable plasmids carrying additional resistance determinants. Apart from the intra-species dissemination, the inter-species exchange of plasmids seems to play an additional important role in the spread of blaNDM. We here present the genetics related to the isolation of three species (Klebsiella pneumoniae, Proteus mirabilis, and Morganella morganii) harboring the blaNDM-1 gene from a single patient in Greece. Bacterial identification and antimicrobial susceptibility testing were performed using the Vitek2. Whole genome sequencing and bioinformatic tools were used to identify resistance genes and plasmids. BlaNDM-1 harboring plasmids were found in all three isolates. Moreover, the plasmid constructs of the respective incomplete or circular contigs showed that the blaNDM-1 and its neighboring genes form a cluster that was found in all isolates. Our microbiological findings, together with the patient's history, suggest the in vivo transfer of the blaNDM-1-containing cluster through three different species in a single patient.

Endocarditis induced by M. morganii in an immunocompetent patient without underlying valvular abnormalities.

Background: The gram-positive cocci is the most common pathogens of infective endocarditis (IE), and it is rarely induced by gram negative bacteria. Only one prior case has been described, in which a patient reported with IE caused by M. morganii, who suffered from multiple myeloma and received high dosages of corticosteroids, chemotherapy and immunomodulatory agents. IE is seldom diagnosed in patients without underlying valvular abnormalities. The most important risk factors of IE are intravenous drug abuse, implanted foreign material and central venous catheterization. Case summary: We describe a case of 34-year-old patient presented to the hospital with recurrent fever and pneumonia since 5 months. He was diagnosed with infective endocarditis with tricuspid vegetation by transthoracic echocardiography (TTE). Two blood culture tests demonstrated the growth of M. morganii, which was further confirmed by a NGS test, as well as a culture of vegetation from the tricuspid. All the evidence confirmed that M. morganii was the causative pathogen of the endocarditis in this case. The IE in an immunocompetent patient without underlying valvular abnormalities had been cured with broad antibiotic therapy and surgical intervention. Conclusion: This was a unique case of IE induced by an extremely rare agent in an immunocompetent patient without underlying valvular abnormalities. Broad-antibiotics with ß-lactam enzyme inhibition should be used on time for M. morganii induced IE with bacteraemia. The operation to curette the vegetation and repair the tricuspid was also an important way to cure the endocarditis in the patient without underlying valvular abnormalities and with repeated episodes of blood stream and lung infections.

Cefoperazone targets D-alanyl-D-alanine carboxypeptidase (DAC) to control Morganella morganii-mediated infection: a subtractive genomic and molecular dynamics approach.

Morganella morganii is a Gram-negative bacterial pathogen that causes bacteremia, urinary tract infections, intra-abdominal infections, chorioamnionitis, neonatal sepsis, and newborn meningitis. To control this bacterial pathogen a total of 3565 putative proteins targets in Morganella morganii were screened using comparative subtractive analysis of biochemical pathways annotated by the KEGG that did not share any similarities with human proteins. One of the targets, D-alanyl-D-alanine carboxypeptidase DacB [Morganella] was observed to be implicated in the majority of cell wall synthesis pathways, leading to its selection as a novel pharmacological target. The drug that interacted optimally with the identified target was observed to be Cefoperazone (DB01329) with the estimated free energy of binding -8.9 Kcal/mol. During molecular dynamics simulations; it was observed that DB01328-2exb and DB01329-2exb complexes showed similar values as the control FMX-2exb complex near 0.2 nm with better stability. Furthermore, MMPBSA total free energy calculation showed better binding energy than the control complex for DB01329-2exb interaction i.e. -31.50 (±0.93) kcal/mol. Our presented research suggested that D-alanyl-D-alanine carboxypeptidase DacB could be a therapeutic target and cefoperazone could be a promising ligand to inhibit the D-alanyl-D-alanine carboxypeptidase DacB protein of Morganella morganii. To identify prospective therapeutic and vaccine targets in Morganella morganii, this is the first computational and subtractive genomics investigation of various metabolic pathways exploring other therapeutic targets of Morganella morganii. In vitro/in vivo experimental validation of the identified target D-alanyl-D-alanine carboxypeptidase and the design of its inhibitors is suggested to figure out the best dose, the drug's effectiveness, and its toxicity.Communicated by Ramaswamy H. Sarma.

Glabridin inhibited the spread of polymyxin-resistant Enterobacterium carrying ICEMmoMP63.

Introduction: The role of integrative and conjugative elements (ICEs) in antibiotic resistance in Morganella morganii is unknown. This study aimed to determine whether an ICE identified in the M. morganii genome contributed to the polymyxin resistance. Methods: Whole-genome sequencing was performed followed by bioinformatics analyses to identify ICEs and antibiotic resistance genes. Conjugation assays were performed to analyze the transferability of a discovered ICE. A drug transporter encoded on the ICE was heterogeneously expressed in Escherichia coli, minimum inhibitory concentrations of antibiotics were determined, and a traditional Chinese medicine library was screened for potential efflux pump inhibitors. Results: An antibiotic resistance-conferring ICE, named ICEMmoMP63, was identified. ICEMmoMP63 was verified to be horizontally transferred among Enterobacteriaceae bacteria. G3577_03020 in ICEMmoMP63 was found to mediate multiple antibiotic resistances, especially polymyxin resistance. However, natural compound glabridin was demonstrated to inhibit polymyxin resistance. Discussion: Our findings support the need for monitoring dissemination of ICEMmoMP63 in Enterobacteriaceae bacteria. Combined glabridin and polymyxin may have therapeutic potential for treating infections from multi-drug resistant bacteria carrying ICEMmoMP63.