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1.
Antibiotics (Basel) ; 11(11)2022 Nov 19.
Article in English | MEDLINE | ID: mdl-36421303

ABSTRACT

Shigellosis is a leading global cause of diarrheal disease and travelers' diarrhea now being complicated by the dissemination of antibiotic resistance, necessitating the development of alternative antibacterials such as therapeutic bacteriophages (phages). Phages with lytic activity against Shigella strains were isolated from sewage. The genomes of 32 phages were sequenced, and based on genomic comparisons belong to seven taxonomic genera: Teetrevirus, Teseptimavirus, Kayfunavirus, Tequatrovirus, Mooglevirus, Mosigvirus and Hanrivervirus. Phage host ranges were determined with a diverse panel of 95 clinical isolates of Shigella from Southeast Asia and other geographic regions, representing different species and serotypes. Three-phage mixtures were designed, with one possessing lytic activity against 89% of the strain panel. This cocktail exhibited lytic activity against 100% of S. sonnei isolates, 97.2% of S. flexneri (multiple serotypes) and 100% of S. dysenteriae serotypes 1 and 2. Another 3-phage cocktail composed of two myophages and one podophage showed both a broad host range and the ability to completely sterilize liquid culture of a model virulent strain S. flexneri 2457T. In a Galleria mellonella model of lethal infection with S. flexneri 2457T, this 3-phage cocktail provided a significant increase in survival.

2.
Infect Drug Resist ; 14: 1-10, 2021.
Article in English | MEDLINE | ID: mdl-33442271

ABSTRACT

PURPOSE: The biology of chronic wounds is complex and many factors act concurrently to impede healing progress. In this study, the dynamics of microflora changes and their antibiotic susceptibility patterns were evaluated longitudinally over 30 days using data from 28 patients with a total of 47 chronic lower extremity wounds. MATERIALS AND METHODS: In this study, colonized wound isolates were characterized using cultural, biochemical, and VITEK 2 methods. Antibiotic susceptibility patterns of the wound isolates were analyzed using various phenotypic assays. Furthermore, antimicrobial resistance patterns and the presence of mutations were evaluated by a genotypic assay, whole-genome sequencing (WGS). RESULTS: Staphylococcus aureus and Pseudomonas aeruginosa were found to be the most common strains at early time points, while members of Enterobacteriaceae were prevalent at later stages of infection. Antimicrobial resistance testing and whole-genome sequencing revealed that the molecular and phenotypic characteristics of the identified wound pathogens remained relatively stable throughout the study period. It was also noted that Enterobacter and Klebsiella species may serve as reservoirs for quinolone resistance in the Pacific region. CONCLUSION: Our observations showed that wounds were colonized with diverse bacteria and interestingly their numbers and/or types were changed over the course of infection. The rapid genetic changes that accompanied the first 4 weeks after presentation did not directly contribute to the development of antibiotic resistance. In addition, standard wound care procedures did not appear to select for resistant bacterial strains. Future efforts should focus on defining those genetic changes associated with the wound colonizing microorganisms that occur beyond 4 weeks.

3.
Fed Pract ; 37(5): 242-246, 2020 May.
Article in English | MEDLINE | ID: mdl-32454579

ABSTRACT

Genetic testing of anaerobic isolates can be important for proper antimicrobial stewardship to identify the appropriate narrow-spectrum treatment for a polymicrobial infection.

4.
Genome Announc ; 3(2)2015 Mar 12.
Article in English | MEDLINE | ID: mdl-25767219

ABSTRACT

Herein we present the draft genome sequence and annotation of "Candidatus Rickettsia asemboensis" strain NMRCii. "Ca. Rickettsia asemboensis" is phylogenetically related to but distinct from the flea-borne spotted fever pathogen Rickettsia felis. "Ca. Rickettsia asemboensis" was initially identified in and subsequently isolated from Ctenocephalides cat and dog fleas from Kenya.

5.
Proc Natl Acad Sci U S A ; 111(51): 18321-6, 2014 Dec 23.
Article in English | MEDLINE | ID: mdl-25489084

ABSTRACT

Environmental factors clearly affect colorectal cancer (CRC) incidence, but the mechanisms through which these factors function are unknown. One prime candidate is an altered colonic microbiota. Here we show that the mucosal microbiota organization is a critical factor associated with a subset of CRC. We identified invasive polymicrobial bacterial biofilms (bacterial aggregates), structures previously associated with nonmalignant intestinal pathology, nearly universally (89%) on right-sided tumors (13 of 15 CRCs, 4 of 4 adenomas) but on only 12% of left-sided tumors (2 of 15 CRCs, 0 of 2 adenomas). Surprisingly, patients with biofilm-positive tumors, whether cancers or adenomas, all had biofilms on their tumor-free mucosa far distant from their tumors. Bacterial biofilms were associated with diminished colonic epithelial cell E-cadherin and enhanced epithelial cell IL-6 and Stat3 activation, as well as increased crypt epithelial cell proliferation in normal colon mucosa. High-throughput sequencing revealed no consistent bacterial genus associated with tumors, regardless of biofilm status. However, principal coordinates analysis revealed that biofilm communities on paired normal mucosa, distant from the tumor itself, cluster with tumor microbiomes as opposed to biofilm-negative normal mucosa bacterial communities also from the tumor host. Colon mucosal biofilm detection may predict increased risk for development of sporadic CRC.


Subject(s)
Colorectal Neoplasms/microbiology , Microbiota , Bacteria/classification , Bacteria/isolation & purification , Biofilms , Colonoscopy , Humans
6.
Antimicrob Agents Chemother ; 58(10): 6151-6, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25092708

ABSTRACT

Tigecycline nonsusceptibility is concerning because tigecycline is increasingly relied upon to treat carbapenem- or colistin-resistant organisms. In Enterobacteriaceae, tigecycline nonsusceptibility is mediated by the AcrAB-TolC efflux pump, among others, and pump activity is often a downstream effect of mutations in their transcriptional regulators, cognate repressor genes, or noncoding regions, as demonstrated in Enterobacteriaceae and Acinetobacter isolates. Here, we report the emergence of tigecycline nonsusceptibility in a longitudinal series of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Klebsiella pneumoniae isolates collected during tigecycline therapy and the elucidation of its resistance mechanisms. Clinical isolates were recovered prior to and during tigecycline therapy of a 2.5-month-old Honduran neonate. Antimicrobial susceptibility tests to tigecycline determined that the MIC increased from 1 to 4 µg/ml prior to the completion of tigecycline therapy. Unlike other studies, we did not find increased expression of ramA, ramR, oqxA, acrB, marA, or rarA genes by reverse transcription-quantitative PCR (qRT-PCR). Whole-genome sequencing revealed an IS5 insertion element in nonsusceptible isolates 85 bp upstream of a putative efflux pump operon, here named kpgABC, previously unknown to be involved in resistance. Introduction of the kpgABC genes in a non-kpgABC background increased the MIC of tigecycline 4-fold and is independent of a functional AcrAB-TolC pump. This is the first report to propose a function for kpgABC and identify an insertion element whose presence correlated with the in vivo development of tigecycline nonsusceptibility in K. pneumoniae.


Subject(s)
Anti-Bacterial Agents/pharmacology , Klebsiella pneumoniae/drug effects , Minocycline/analogs & derivatives , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Drug Resistance, Bacterial/genetics , Microbial Sensitivity Tests , Minocycline/pharmacology , Molecular Sequence Data , Tigecycline
7.
Antimicrob Agents Chemother ; 57(5): 2413-6, 2013 May.
Article in English | MEDLINE | ID: mdl-23478957

ABSTRACT

Klebsiella pneumoniae strain MRSN2404 was isolated from the chronic wound of a soldier who had been wounded in Iraq in 2006. The strain displayed very high MICs of all aminoglycosides, including arbekacin. A gene encoding a novel 16S rRNA methyltransferase, now designated RmtH, was identified. RmtH had 64% identity with RmtB1 and RmtB2. rmtH was bracketed by two copies of ISCR2, which may have played a role in its mobilization.


Subject(s)
Aminoglycosides/pharmacology , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Klebsiella pneumoniae/genetics , Methyltransferases/metabolism , RNA, Ribosomal, 16S/metabolism , Amino Acid Sequence , Bacterial Proteins/genetics , Drug Resistance, Multiple, Bacterial/drug effects , Humans , Iraq , Isoenzymes/genetics , Isoenzymes/metabolism , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Klebsiella pneumoniae/enzymology , Klebsiella pneumoniae/isolation & purification , Male , Methyltransferases/genetics , Microbial Sensitivity Tests , Molecular Sequence Data , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Homology, Amino Acid , Warfare
8.
Plant J ; 41(2): 212-20, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15634198

ABSTRACT

Previous studies have indicated that Arabidopsis thaliana experienced a genome-wide duplication event shortly before its divergence from Brassica followed by extensive chromosomal rearrangements and deletions. While a large number of the duplicated genes have significantly diverged or lost their sister genes, we found 4222 pairs that are still highly conserved, and as a result had similar functional assignments during the annotation of the genome sequence. Using whole-genome DNA microarrays, we identified 906 duplicated gene pairs in which at least one member exhibited a significant response to oxidative stress. Among these, only 117 pairs were up- or down-regulated in both pairs and many of these exhibited dissimilar patterns of expression. Examination of the expression patterns of PAL1 and PAL2, ACD1 and ACD2, genes coding for two Hsp20s, various P450s, and electron transfer flavoproteins suggests Arabidopsis evolved a number of distinct oxidative stress response mechanisms using similar gene sets following the duplication of its genome.


Subject(s)
Arabidopsis Proteins/genetics , Arabidopsis/genetics , Gene Duplication , Genetic Variation , Genome, Plant , Oxidative Stress , Transcription, Genetic , Chromosome Mapping , Gene Expression Regulation, Plant , Oligonucleotide Array Sequence Analysis
9.
Mol Microbiol ; 51(4): 1051-70, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14763980

ABSTRACT

Natural genetic transformation in Streptococcus pneumoniae is controlled in part by a quorum-sensing system mediated by a peptide pheromone called competence-stimulating peptide (CSP), which acts to coordinate transient activation of genes required for competence. To characterize the transcriptional response and regulatory events occurring when cells are exposed to competence pheromone, we constructed DNA microarrays and analysed the temporal expression profiles of 1817 among the 2129 unique predicted open reading frames present in the S. pneumoniae TIGR4 genome (84%). After CSP stimulation, responsive genes exhibited four temporally distinct expression profiles: early, late and delayed gene induction, and gene repression. At least eight early genes participate in competence regulation including comX, which encodes an alternative sigma factor. Late genes were dependent on ComX for CSP-induced expression, many playing important roles in transformation. Genes in the delayed class (third temporal wave) appear to be stress related. Genes repressed during the CSP response include ribosomal protein loci and other genes involved in protein synthesis. This study increased the number of identified CSP-responsive genes from approximately 40 to 188. Given the relatively large number of induced genes (6% of the genome), it was of interest to determine which genes provide functions essential to transformation. Many of the induced loci were subjected to gene disruption mutagenesis, allowing us to establish that among 124 CSP-inducible genes, 67 were individually dispensable for transformation, whereas 23 were required for transformation.


Subject(s)
Bacterial Proteins/physiology , DNA-Binding Proteins/physiology , Gene Expression Regulation, Bacterial , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/physiology , Transformation, Bacterial , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Bacterial Proteins/pharmacology , DNA-Binding Proteins/pharmacology , Gene Deletion , Gene Expression Profiling , Genes, Bacterial , Oligonucleotide Array Sequence Analysis , Peptide Biosynthesis/genetics , Peptide Biosynthesis/physiology , Pheromones/pharmacology , Pheromones/physiology , RNA, Bacterial/analysis , RNA, Bacterial/genetics , RNA, Messenger/analysis , RNA, Messenger/genetics , Ribosomal Proteins/genetics , Ribosomal Proteins/physiology , Time Factors , Transcription Factors/genetics , Transcription Factors/metabolism , Transcriptional Activation
10.
Genome Res ; 13(3): 327-40, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12618363

ABSTRACT

The gene predictions and accompanying functional assignments resulting from the sequencing and annotation of a genome represent hypotheses that can be tested and used to develop a more complete understanding of the organism and its biology. In the model plant Arabidopsis thaliana, we developed a novel approach to constructing whole-genome microarrays based on PCR amplification of the 3' ends of each predicted gene from genomic DNA, and constructed an array representing more than 94% of the predicted genes and pseudogenes on chromosome 2. With this array, we examined various tissues and physiological conditions, providing expression-based validation for 84% of the gene predictions and providing clues as to the functions of many predicted genes. Further, by examining the distribution of expression along the physical chromosome, we were able to identify a region of repressed transcription that may represent a previously undescribed heterochromatic region.


Subject(s)
Arabidopsis/genetics , Chromosomes, Plant/genetics , DNA, Plant/genetics , Gene Expression Profiling/methods , Nucleic Acid Amplification Techniques/methods , Oligonucleotide Array Sequence Analysis/methods , Arabidopsis/microbiology , Arabidopsis/physiology , Bacterial Infections/genetics , Cold Temperature , Gene Expression Regulation, Plant/physiology , Gene Targeting/methods , Genes, Plant/physiology , Hot Temperature , Organ Specificity/genetics , Plant Diseases/microbiology , Plant Structures/genetics , Plant Structures/microbiology , Plant Structures/physiology , Salts
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