scholarly journals Efficacy of the Endolysin-Based Antibacterial Gel for Treatment of Anaerobic Infection Caused by Fusobacterium necrophorum

Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1260
Author(s):  
Daria V. Vasina ◽  
Nataliia P. Antonova ◽  
Aleksei M. Vorobev ◽  
Aleksei I. Laishevtsev ◽  
Andrei V. Kapustin ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Acute Inflammation ◽  
Bacterial Species ◽  
Systemic Infection ◽  
Fold Increase ◽  
Fusobacterium Necrophorum ◽  
Abscess Formation ◽  
Gram Negative ◽  
Gel Treatment ◽  
Life Threatening

Abscess formation is a common complication of severe life-threatening infections caused by obligate anaerobes. Fusobacterium necrophorum is among the frequently detected anaerobic pathogens from clinical specimens associated with liver abscesses, skin and soft tissue infections, or oral abscesses. The antimicrobial therapy for this kind of infection needs to be optimized. Here, we examined the possibility of treating F. necrophorum-induced abscess wound infections with candidate therapeutics based on three endolysins with activity against a broad spectrum of aerobe Gram-negative pathogens. Antibacterial gel containing three Gram-negative bacteria-targeting endolysins, LysAm24, LysAp22, and LysECD7, was formulated for topical use. Abscess formation was induced in rabbits with F. necrophorum and caused systemic infection. The survival and lifespan of the animals, general parameters, and biochemical and hematological blood tests were analyzed to assess the effectiveness of the gel treatment for the wound infection. The administration of the investigated gel twice per day for 5 days resulted in less acute inflammation, with decreased leukocytes and segmented neutrophils in the blood, retardation of infection progression, and an almost two-fold increase in the lifespan of the animals compared to the placebo group. The results indicate that endolysin-based therapy is an effective approach to treat anaerobic bacterial infections. The use of endolysins as independent pharmaceuticals, or their combination with antibiotics, could significantly reduce the development of complications in infectious diseases caused by sensitive bacterial species.

scholarly journals The Meningococcal ABC-Type l-Glutamate Transporter GltT Is Necessary for the Development of Experimental Meningitis in Mice

2009 ◽  
Vol 77 (9) ◽  
pp. 3578-3587 ◽  
Author(s):  
Roberta Colicchio ◽  
Susanna Ricci ◽  
Florentia Lamberti ◽  
Caterina Pagliarulo ◽  
Chiara Pagliuca ◽  
...  
Keyword(s):  
Histological Analysis ◽  
Glutamate Uptake ◽  
Glutamate Transporter ◽  
Systemic Infection ◽  
Fold Increase ◽  
Wild Type ◽  
Nutrient Source ◽  
Infectious Dose ◽  
Life Threatening ◽  
The Brain

ABSTRACT Experimental animal models of bacterial meningitis are useful to study the host-pathogen interactions occurring at the cerebral level and to analyze the pathogenetic mechanisms behind this life-threatening disease. In this study, we have developed a mouse model of meningococcal meningitis based on the intracisternal inoculation of bacteria. Experiments were performed with mouse-passaged serogroup C Neisseria meningitidis. Survival and clinical parameters of infected mice and microbiological and histological analysis of the brain demonstrated the establishment of meningitis with features comparable to those of the disease in humans. When using low bacterial inocula, meningococcal replication in the brain was very efficient, with a 1,000-fold increase of viable counts in 18 h. Meningococci were also found in the blood, spleens, and livers of infected mice, and bacterial loads in different organs were dependent on the infectious dose. As glutamate uptake from the host has been implicated in meningococcal virulence, mice were infected intracisternally with an isogenic strain deficient in the ABC-type l-glutamate transporter GltT. Noticeably, the mutant was attenuated in virulence in mixed infections, indicating that wild-type bacteria outcompeted the GltT-deficient meningococci. The data show that the GltT transporter plays a role in meningitis and concomitant systemic infection, suggesting that meningococci may use l-glutamate as a nutrient source and as a precursor to synthesize the antioxidant glutathione.

scholarly journals Antibacterial and Antibiotic Modifying Potential of Crude Extracts, Fractions, and Compounds from Acacia polyacantha Willd. against MDR Gram-Negative Bacteria

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Flora T. Mambe ◽  
Jean Na-Iya ◽  
Ghislain W. Fotso ◽  
Fred Ashu ◽  
Bathélémy Ngameni ◽  
...  
Keyword(s):  
Oleanolic Acid ◽  
Bacterial Infections ◽  
Efflux Pump ◽  
Synergistic Effects ◽  
Bacterial Species ◽  
Gram Negative Bacteria ◽  
Efflux Pump Inhibitor ◽  
Gram Negative ◽  
Acacia Polyacantha

The present study aimed to assess the in vitro antibacterial and antibiotic modifying activities of methanol extracts prepared from the leaf (APL) and bark (APB) of Acacia polyacantha, fractions (APLa-d) and compounds isolated from APL against a panel of multidrug resistant (MDR) Gram-negative bacteria. Leaf extract was subjected to column chromatography for compounds isolation; antibacterial assays were performed on samples alone and with an efflux pump inhibitor (EPI), respectively, and several antibiotics on the tested bacteria. The phytochemical investigation of APL led to the isolation of stigmasterol (1), β-amyrin (2), 3-O-β-D-glucopyranosylstigmasterol (3), 3-O-methyl-D-chiro-inositol (4), epicatechin (5), quercetin-3-O-glucoside (6), 3-O-[β-D-xylopyranosyl-(1→4)-β-D-galactopyranosyl]-oleanolic acid (7), and 3-O-[β-galactopyranosyl-(1→4)-β-D-galactopyranosyl]-oleanolic acid (8). APL and APB had minimal inhibitory concentration (MIC) values ≤ 1024 μg/mL on 73.3% and 46.7% of the tested bacteria, respectively. APLb and APLd were effective against 88.9% of tested bacterial species with compound 8 showing the highest activity inhibiting 88.9% of tested bacteria. The EPI, phenylalanine-arginine-β-naphthylamide (PAßN), strongly improved the activity of APL, APLb, APLd, and compound 8 on all tested bacteria. Synergistic effects were obtained when APL and compounds 7 and 8 were combined with erythromycin (ERY), gentamycin (GEN), ciprofloxacin (CIP), and norfloxacin (NOR). The present study demonstrates the antibacterial potential of Acacia polyacantha and its constituents to combat bacterial infections alone or in combination with EPI.

Gram-negative Bacteremia in Four Patients With Klippel-Trenaunay-Weber Syndrome

PEDIATRICS ◽  
1996 ◽  
Vol 97 (5) ◽  
pp. 739-741
Author(s):  
Lynne M. Bird ◽  
Marilyn C. Jones ◽  
Nathan Kuppermann ◽  
W. Charles Huskins
Keyword(s):  
Soft Tissues ◽  
Systemic Infection ◽  
Invasive Infection ◽  
Gram Negative ◽  
Weber Syndrome ◽  
Gram Negative Bacteremia ◽  
Life Threatening ◽  
Life Threatening Complication ◽  
Gram Negative Organisms ◽  
Congenital Malformation Syndrome

Klippel-Trenaunay-Weber syndrome (KTWS) is a sporadically occurring congenital malformation syndrome consisting of hemangiomata, venous varicosities, and hypertrophy of soft tissues and/or overgrowth of bone.1-3 Although the list of potential complications is long, KTWS is generally a nonprogressive condition. The problems, which include edema, stasis dermatitis, skin ulceration, cellulitis, anemia, thrombosis, phleboliths, phlebitis, bone and joint abnormalities, scoliosis, and paresthesias, tend to be chronic in nature.4 Recognized life-threatening complications include disseminated intravascular coagulation (DIC)5 and gastrointestinal bleeding as a result of hemangiomata in the intestine.6,7 Systemic infection has not been reported as a major cause of morbidity and mortality. The purpose of this report is to present 4 patients with KTWS who had invasive infection with gram-negative organisms to document another life-threatening complication of this syndrome.

scholarly journals Diversity and Proliferation of Metallo-β-Lactamases: a Clarion Call for Clinically Effective Metallo-β-Lactamase Inhibitors

2018 ◽  
Vol 84 (18) ◽  
Author(s):  
Anou M. Somboro ◽  
John Osei Sekyere ◽  
Daniel G. Amoako ◽  
Sabiha Y. Essack ◽  
Linda A. Bester
Keyword(s):  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Structural Variations ◽  
Gram Negative ◽  
Clinical Phase ◽  
Class B ◽  
Life Threatening ◽  
Made In

ABSTRACTThe worldwide proliferation of life-threatening metallo-β-lactamase (MBL)-producing Gram-negative bacteria is a serious concern to public health. MBLs are compromising the therapeutic efficacies of β-lactams, particularly carbapenems, which are last-resort antibiotics indicated for various multidrug-resistant bacterial infections. Inhibition of enzymes mediating antibiotic resistance in bacteria is one of the major promising means for overcoming bacterial resistance. Compounds having potential MBL-inhibitory activity have been reported, but none are currently under clinical trials. The need for developing safe and efficient MBL inhibitors (MBLIs) is obvious, particularly with the continuous spread of MBLs worldwide. In this review, the emergence and escalation of MBLs in Gram-negative bacteria are discussed. The relationships between different class B β-lactamases identified up to 2017 are represented by a phylogenetic tree and summarized. In addition, approved and/or clinical-phase serine β-lactamase inhibitors are recapitulated to reflect the successful advances made in developing class A β-lactamase inhibitors. Reported MBLIs, their inhibitory properties, and their purported modes of inhibition are delineated. Insights into structural variations of MBLs and the challenges involved in developing potent MBLIs are also elucidated and discussed. Currently, natural products and MBL-resistant β-lactam analogues are the most promising agents that can become clinically efficient MBLIs. A deeper comprehension of the mechanisms of action and activity spectra of the various MBLs and their inhibitors will serve as a bedrock for further investigations that can result in clinically useful MBLIs to curb this global menace.

scholarly journals The Novel Immunotherapeutic Oligodeoxynucleotide IMT504 Protects Neutropenic Animals from Fatal Pseudomonas aeruginosa Bacteremia and Sepsis

2014 ◽  
Vol 59 (2) ◽  
pp. 1225-1229 ◽  
Author(s):  
Abdullah Chahin ◽  
Steven M. Opal ◽  
Jorge Zorzopulos ◽  
David V. Jobes ◽  
Yazan Migdady ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Academic Research ◽  
Systemic Infection ◽  
Oral Feeding ◽  
Survival Advantage ◽  
Therapeutic Interventions ◽  
Sprague Dawley ◽  
Gram Negative ◽  
Content Type

ABSTRACTIMT504 is a novel immunomodulatory oligonucleotide that has shown immunotherapeutic properties in early preclinical and clinical studies. IMT504 was tested in a neutropenic rat model ofPseudomonas aeruginosabacteremia and sepsis. This animal system recapitulates many of the pathological processes found in neutropenic patients with Gram-negative, bacterial infections. The research was conducted in the setting of an academic research laboratory. The test subjects were Sprague-Dawley rats. Animals were rendered neutropenic by administration of cyclophosphamide, colonized withP. aeruginosaby oral feeding, and then randomized to receive IMT504 over a range of doses and treatment regimens representing early and late therapeutic interventions. IMT504 immunotherapy conferred a significant survival advantage over the 12-day study period compared with the results seen with placebo-treated animals when the therapy was administered at the onset of neutropenia and even in the absence of antibiotics and after the onset of fever and systemic infection. Notably, even late salvage IMT504 monotherapy was highly effective (13/14 surviving rats with IMT504 therapy versus 2/14 controls,P= <0.001). Moreover, late salvage IMT504 monotherapy was as effective as antibiotic therapy (13/14 surviving rats versus 21/21 rats,P= 0.88). In addition, no antagonism or loss of therapeutic efficacy was noted with combination therapy of IMT504 plus antibiotics. IMT504 immunotherapy provides a remarkable survival advantage in bacteremia and sepsis in neutropenic animals and deserves further study as a new treatment option in patients with, or at risk for, severe Gram-negative bacterial infections and sepsis.

scholarly journals Prevalence and Antibiotic Sensitivity pattern of Bacterial Isolates from Catheterized UTI Patients: A Local Study

2021 ◽  
Vol 2 (2) ◽  
pp. 229-235
Author(s):  
Iqra Arooj ◽  
Alishba Sehar ◽  
Asghar Javaid
Keyword(s):  
Bacterial Infections ◽  
Bacterial Species ◽  
Local Population ◽  
Bacterial Isolates ◽  
Biochemical Tests ◽  
Gram Positive ◽  
Local Study ◽  
Gram Negative ◽  
Sensitivity Pattern ◽  
Tract Infections

Prevalence and multidrug resistance among bacteria in catheter-associated urinary tract infections (CAUTIs) has been on the rise in recent times. Hence, the prevalence rate and antibacterial susceptibility of bacteria in CAUTIs in ICU patients was evaluated. A total of 120 patients admitted to the ICU of Nishtar Hospital, Multan, were recruited for this study. Both gram-positive and gram-negative bacterial isolates were characterized based on biochemical tests including catalase test, oxidase test, indole test, TSI test, citrate test, coagulase test and growth on 6.5% NaCl agar. The prevalence of bacterial species was Escherichia coli (32%), Staphylococcus aureus (26%), Pseudomonas spp. (18%), Proteus spp. (14%) and Enterococcus spp. (2%). A considerable degree of resistance against commonly prescribed antibiotics was observed. Gram negative bacteria showed resistance to ciprofloxacin, piperacillin-tazobactam and amikacin as well as susceptibility to imipenem, tigecycline and polymixin. Gram positive bacteria showed resistance to antibiotics such as piperacillin-tazobactam, ampicillin, gentamicin, oxacillin and ceftazidime suggesting the ineffectiveness of these antibiotics for treating bacterial infections among CAUTI patients and demonstrating the latest trends in antimicrobial drug resistance profile in local population.

The effect of exosomes derived from unrestricted somatic stem cells on murine model of sepsis

2021 ◽  
Author(s):  
Mahshid Akhavan Rahnama ◽  
Mina Soufi Zomorrod ◽  
Saeid Abroun ◽  
Amir Atashi
Keyword(s):  
Stem Cells ◽  
Mouse Model ◽  
Bacterial Infections ◽  
Direct Injection ◽  
Systemic Infection ◽  
Fold Increase ◽  
Somatic Stem Cells ◽  
Novel Therapy ◽  
Human Cord Blood ◽  
Unrestricted Somatic Stem Cells

Sepsis is a systemic infection mainly caused by bacterial infections. Despite all efforts and advances in treatment of sepsis, it's still considered as one of the leading causes of death in the hospitalized patients. Today we have to use novel therapies and one of the most important is cell free therapy. Exosomes have been introduced to have all cell contents without compatible tissue complex proteins which is a good candidate for transplantation. Unrestricted somatic stem cells (USSC) also known as mesenchymal stem cell progenitors due to their high proliferative capacity and low immune response, which is a novel therapy for sepsis. In this study, the effect of USSC-derived exosomes on sepsis was investigated using a mouse model. USSCs were isolated from human cord blood and characterized by flow cytometry and multilineage differentiation. The exosomes were then harvested from USSCs and characterized by transmission electron microscopy, Western blotting, and dynamic light scattering. The harvested exosomes were injected into the mouse model of sepsis. Biochemical, histological, molecular, and survival studies were performed in different groups. Our observation showed that USSC-derived exosomes can reduce inflammation in septic mice. Histopathological and biochemical findings in the sham group obviously showed multiorgan involvement, but these changes disappeared after seven days of exosome administration. Moreover, the expression of IRAK-1 and TRAF-6 (main adapter molecules in signaling pathways of inflammation) was decreased through negative regulation by miR-146a after 72 h of exosome administration; finally, it leads to a 2-fold increase in the level of IL-10 and a 2-fold decrease in the levels of IL-6 and TNF-α . In conclusion, we reported that direct injection of USSC- derived exosomes can be one of the important methods for the treatment of various aspects of sepsis due to their immunomodulatory properties.

scholarly journals Evolution and Dissemination of OqxAB-Like Efflux Pumps, an Emerging Quinolone Resistance Determinant among Members of Enterobacteriaceae

2015 ◽  
Vol 59 (6) ◽  
pp. 3290-3297 ◽  
Author(s):  
Marcus Ho Yin Wong ◽  
Edward Wai Chi Chan ◽  
Sheng Chen
Keyword(s):  
Efflux Pump ◽  
Phylogenetic Analyses ◽  
Bacterial Species ◽  
Fold Increase ◽  
Quinolone Resistance ◽  
Cross Resistance ◽  
Phenotypic Characteristics ◽  
Gram Negative ◽  
Content Type ◽  
Elevated Expression

ABSTRACTThe OqxAB efflux pump, a plasmid-mediated quinolone resistance (PMQR) determinant, has become increasingly prevalent among members ofEnterobacteriaceaeover the past decade. To investigate the evolution and dissemination routes of theoqxABoperon, we assessed the prevalence ofoqxAB-like elements among various Gram-negative bacterial species and analyzed the genotypic and phenotypic characteristics of organisms harboring such elements. With a comprehensive genotyping approach, a chromosome-basedoqxABoperon was detectable in allKlebsiella pneumoniaestrains tested, including organisms isolated before the year 1984. Sequence and phylogenetic analyses confirmed that theoqxABoperon inK. pneumoniaeisolates was genetically closest to their plasmid-borne counterparts recoverable only fromEscherichia coliandSalmonellaisolates collected from the year 2003 onward. Chromosomal elements with much lower sequence homology were also found among theEnterobacterspp. but not other Gram-negative species. Contrary to the quinolone resistance phenotypes which were consistently observable among organisms withoqxAB-harboring plasmids, chromosomaloqxABelements generally did not confer quinolone resistance, except forK. pneumoniaestrains, which exhibited a typicaloqxAB-mediated phenotype characterized by cross-resistance to olaquindox, chloramphenicol, and the quinolones. Gene expression analysis illustrated that such phenotypes were due to elevated expression of the chromosomaloqxABoperon. Furthermore, transposition of theoqxABoperon from the bacterial chromosome to plasmids was found to result in a >80-fold increase in the level of expression of the OqxAB pump, confirming its status as the first constitutively expressed efflux system located in bacterial mobile elements.

Characterizing and Overcoming Resistance to Aminomethylspectinomycins in Gram-negative Bacteria

2021 ◽  
Author(s):  
◽  
Nisha Das ◽  
Keyword(s):  
Small Molecule ◽  
Legionella Pneumophila ◽  
Bacterial Infections ◽  
Enzyme Assay ◽  
Bacterial Species ◽  
Enteric Bacteria ◽  
Response Analysis ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
E Coli

Spectinomycin (SPC) is a broad-spectrum aminocyclitol antibiotic. Its use in agriculture has led to widespread resistance in enteric bacteria, necessitating the development of more effective analogs. Aminomethyl spectinomycins (amSPC) are modified spectinomycins with increased potency against many bacterial species. These species include Legionella pneumophila, which harbors a chromosomally encoded aminoglycoside modifying enzyme (AME). In this study, we follow up on this observation and examine the extent to which the amSPCs are substrates for AMEs through adenylation (ANTs) and phosphorylation (APH). APH(9)-Ia and ANT(3")(9) were expressed in E. coli BL21(DE3) and purified using the Ni-affinity chromatography. The ability of AMEs to modify and inactivate amSPCs has been examined by two unique biochemical assays, including an agar-based enzyme assay. Binding of APH (9)-Ia and ANT (3")(9) to spectinomycin and amSPCs has been studied using Thermal Denaturation assay and MicroScale Thermophoresis (MST). The microbiological role of these enzymes has been examined by minimum inhibitory concentration (MIC) shifts using an arabinose inducible expression of APH (9)-Ia and ANT (3")(9) in E.coli K12 and JW ΔtolC strains. Our agar-based enzyme assay shows the inactivation of spectinomycin by APH(9)-Ia. Phosphorylated spectinomycin and adenylated spectinomycin products upon incubation with APH(9)-Ia and ANT(3",9), respectively, have been identified using MALDI-MS. APH(9)-Ia induction studies in E. coli tolC knock-out strains reveal a MIC increase against spectinomycin in the presence of 2% arabinose compared to no shift with amSPCs. ANT (3")(9) showed an increase in MIC against spectinomycin as well as amSPCs. In conclusion, amSPCs are not inactivated by APH (9)-Ia in vivo but are inactivated by ANT (3")(9). Most Gram-negative bacteria isolated in clinics possess one or more AMEs. By overcoming modification by AMEs, amSPCs can be a valuable tool in overcoming resistance in Gram-negative bacterial infections. We also conducted a high throughput screen of a polar small molecule library against two multi-drug resistant clinical isolates of Escherichia coli that encode aminoglycoside modifying enzyme for small molecule potentiators of amSPCs to yield 12 possible potentiating molecules that have been confirmed by dose-response analysis. Future work as a continuation of this project will involve further analysis of any existing synergy between the potentiating molecules and amSPCs and target validation of these potentiators.

scholarly journals BacCapSeq: a Platform for Diagnosis and Characterization of Bacterial Infections

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Orchid M. Allicock ◽  
Cheng Guo ◽  
Anne-Catrin Uhlemann ◽  
Susan Whittier ◽  
Lokendra V. Chauhan ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
High Throughput ◽  
Bacterial Infections ◽  
High Throughput Sequencing ◽  
Limit Of Detection ◽  
Bacterial Species ◽  
Fold Increase ◽  
Virulence Determinants ◽  
Antimicrobial Resistance Genes

ABSTRACT We report a platform that increases the sensitivity of high-throughput sequencing for detection and characterization of bacteria, virulence determinants, and antimicrobial resistance (AMR) genes. The system uses a probe set comprised of 4.2 million oligonucleotides based on the Pathosystems Resource Integration Center (PATRIC) database, the Comprehensive Antibiotic Resistance Database (CARD), and the Virulence Factor Database (VFDB), representing 307 bacterial species that include all known human-pathogenic species, known antimicrobial resistance genes, and known virulence factors, respectively. The use of bacterial capture sequencing (BacCapSeq) resulted in an up to 1,000-fold increase in bacterial reads from blood samples and lowered the limit of detection by 1 to 2 orders of magnitude compared to conventional unbiased high-throughput sequencing, down to a level comparable to that of agent-specific real-time PCR with as few as 5 million total reads generated per sample. It detected not only the presence of AMR genes but also biomarkers for AMR that included both constitutive and differentially expressed transcripts. IMPORTANCE BacCapSeq is a method for differential diagnosis of bacterial infections and defining antimicrobial sensitivity profiles that has the potential to reduce morbidity and mortality, health care costs, and the inappropriate use of antibiotics that contributes to the development of antimicrobial resistance.

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