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Article ; Online: Association between baseline abundance of Peptoniphilus, a Gram-positive anaerobic coccus, and wound healing outcomes of DFUs.

Min, Kyung R / Galvis, Adriana / Baquerizo Nole, Katherine L / Sinha, Rohita / Clarke, Jennifer / Kirsner, Robert S / Ajdic, Dragana

PloS one

2020 Volume 15, Issue 1, Page(s) e0227006

Abstract: Diabetic foot ulcers (DFUs) lead to nearly 100,000 lower limb amputations annually in the United States. DFUs are colonized by complex microbial communities, and infection is one of the most common reasons for diabetes-related hospitalizations and ... ...

Abstract	Diabetic foot ulcers (DFUs) lead to nearly 100,000 lower limb amputations annually in the United States. DFUs are colonized by complex microbial communities, and infection is one of the most common reasons for diabetes-related hospitalizations and amputations. In this study, we examined how DFU microbiomes respond to initial sharp debridement and offloading and how the initial composition associates with 4 week healing outcomes. We employed 16S rRNA next generation sequencing to perform microbial profiling on 50 samples collected from 10 patients with vascularized neuropathic DFUs. Debrided wound samples were obtained at initial visit and after one week from two DFU locations, wound bed and wound edge. Samples of the foot skin outside of the wounds were also collected for comparison. We showed that DFU wound beds are colonized by a greater number of distinct bacterial phylotypes compared to the wound edge or skin outside the wound. However, no significant microbiome diversity changes occurred at the wound sites after one week of standard care. Finally, increased initial abundance of Gram-positive anaerobic cocci (GPAC), especially Peptoniphilus (p < 0.05; n = 5 subjects), was associated with impaired healing; thus, GPAC's abundance could be a predictor of the wound-healing outcome.
MeSH term(s)	Aged ; Bacteria, Anaerobic ; Debridement/methods ; Diabetic Foot/complications ; Diabetic Foot/microbiology ; Female ; Foot Ulcer/microbiology ; Gram-Positive Bacterial Infections ; Gram-Positive Cocci/isolation & purification ; Humans ; Male ; Microbiota ; Middle Aged ; Predictive Value of Tests ; Treatment Outcome ; Wound Healing
Language	English
Publishing date	2020-01-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0227006
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Article: Global transcriptional analysis of Streptococcus mutans sugar transporters using microarrays.

Ajdić, Dragana / Pham, Vi T T

Journal of bacteriology

2007 Volume 189, Issue 14, Page(s) 5049–5059

Abstract: The transport of carbohydrates by Streptococcus mutans is accomplished by the phosphoenolpyruvate-phosphotransferase system (PTS) and ATP-binding cassette (ABC) transporters. To undertake a global transcriptional analysis of all S. mutans sugar ... ...

Abstract	The transport of carbohydrates by Streptococcus mutans is accomplished by the phosphoenolpyruvate-phosphotransferase system (PTS) and ATP-binding cassette (ABC) transporters. To undertake a global transcriptional analysis of all S. mutans sugar transporters simultaneously, we used a whole-genome expression microarray. Global transcription profiles of S. mutans UA159 were determined for several monosaccharides (glucose, fructose, galactose, and mannose), disaccharides (sucrose, lactose, maltose, and trehalose), a beta-glucoside (cellobiose), oligosaccharides (raffinose, stachyose, and maltotriose), and a sugar alcohol (mannitol). The results revealed that PTSs were responsible for transport of monosaccharides, disaccharides, beta-glucosides, and sugar alcohol. Six PTSs were transcribed only if a specific sugar was present in the growth medium; thus, they were regulated at the transcriptional level. These included transporters for fructose, lactose, cellobiose, and trehalose and two transporters for mannitol. Three PTSs were repressed under all conditions tested. Interestingly, five PTSs were always highly expressed regardless of the sugar source used, presumably suggesting their availability for immediate uptake of most common dietary sugars (glucose, fructose, maltose, and sucrose). The ABC transporters were found to be specific for oligosaccharides, raffinose, stachyose, and isomaltosaccharides. Compared to the PTSs, the ABC transporters showed higher transcription under several tested conditions, suggesting that they might be transporting multiple substrates.
MeSH term(s)	ATP-Binding Cassette Transporters/genetics ; ATP-Binding Cassette Transporters/metabolism ; ATP-Binding Cassette Transporters/physiology ; Biological Transport/genetics ; Carbohydrates/pharmacokinetics ; Cellobiose/metabolism ; Cellobiose/pharmacokinetics ; Fructose/metabolism ; Fructose/pharmacokinetics ; Galactose/metabolism ; Galactose/pharmacokinetics ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Glucose/metabolism ; Glucose/pharmacokinetics ; Lactose/metabolism ; Lactose/pharmacokinetics ; Maltose/metabolism ; Maltose/pharmacokinetics ; Mannose/metabolism ; Mannose/pharmacokinetics ; Oligonucleotide Array Sequence Analysis/methods ; Oligosaccharides/metabolism ; Oligosaccharides/pharmacokinetics ; Phosphoenolpyruvate Sugar Phosphotransferase System/genetics ; Phosphoenolpyruvate Sugar Phosphotransferase System/metabolism ; Phosphoenolpyruvate Sugar Phosphotransferase System/physiology ; Raffinose/metabolism ; Raffinose/pharmacokinetics ; Reverse Transcriptase Polymerase Chain Reaction ; Streptococcus mutans/genetics ; Streptococcus mutans/metabolism ; Sucrose/metabolism ; Sucrose/pharmacokinetics ; Transcription, Genetic ; Trisaccharides/metabolism ; Trisaccharides/pharmacokinetics
Chemical Substances	Carbohydrates ; Oligosaccharides ; Trisaccharides ; Cellobiose (16462-44-5) ; stachyose (25VX64653N) ; Fructose (30237-26-4) ; Sucrose (57-50-1) ; maltotriose (639K0T34IK) ; Maltose (69-79-4) ; Phosphoenolpyruvate Sugar Phosphotransferase System (EC 2.7.1.-) ; Glucose (IY9XDZ35W2) ; Lactose (J2B2A4N98G) ; Raffinose (N5O3QU595M) ; Mannose (PHA4727WTP) ; Galactose (X2RN3Q8DNE)
Language	English
Publishing date	2007-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/JB.00338-07
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Article ; Online: Antibacterial and Antibiofilm Activities of a Novel Synthetic Cyclic Lipopeptide against Cariogenic Streptococcus mutans UA159.

Min, Kyung R / Galvis, Adriana / Williams, Brandon / Rayala, Ramanjaneyulu / Cudic, Predrag / Ajdic, Dragana

Antimicrobial agents and chemotherapy

2017 Volume 61, Issue 8

Abstract: Despite continuous efforts to control cariogenic dental biofilms, very few effective antimicrobial treatments exist. In this study, we characterized the activity of the novel synthetic cyclic lipopeptide 4 (CLP-4), derived from fusaricidin, against the ... ...

Abstract	Despite continuous efforts to control cariogenic dental biofilms, very few effective antimicrobial treatments exist. In this study, we characterized the activity of the novel synthetic cyclic lipopeptide 4 (CLP-4), derived from fusaricidin, against the cariogenic pathogen
Language	English
Publishing date	2017-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/AAC.00776-17
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Article ; Online: Association between baseline abundance of Peptoniphilus, a Gram-positive anaerobic coccus, and wound healing outcomes of DFUs.

Kyung R Min / Adriana Galvis / Katherine L Baquerizo Nole / Rohita Sinha / Jennifer Clarke / Robert S Kirsner / Dragana Ajdic

PLoS ONE, Vol 15, Iss 1, p e

2020 Volume 0227006

Abstract	Diabetic foot ulcers (DFUs) lead to nearly 100,000 lower limb amputations annually in the United States. DFUs are colonized by complex microbial communities, and infection is one of the most common reasons for diabetes-related hospitalizations and amputations. In this study, we examined how DFU microbiomes respond to initial sharp debridement and offloading and how the initial composition associates with 4 week healing outcomes. We employed 16S rRNA next generation sequencing to perform microbial profiling on 50 samples collected from 10 patients with vascularized neuropathic DFUs. Debrided wound samples were obtained at initial visit and after one week from two DFU locations, wound bed and wound edge. Samples of the foot skin outside of the wounds were also collected for comparison. We showed that DFU wound beds are colonized by a greater number of distinct bacterial phylotypes compared to the wound edge or skin outside the wound. However, no significant microbiome diversity changes occurred at the wound sites after one week of standard care. Finally, increased initial abundance of Gram-positive anaerobic cocci (GPAC), especially Peptoniphilus (p < 0.05; n = 5 subjects), was associated with impaired healing; thus, GPAC's abundance could be a predictor of the wound-healing outcome.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Wound biofilms: lessons learned from oral biofilms.

Mancl, Kimberly A / Kirsner, Robert S / Ajdic, Dragana

Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society

2013 Volume 21, Issue 3, Page(s) 352–362

Abstract: Biofilms play an important role in the development and pathogenesis of many chronic infections. Oral biofilms, more commonly known as dental plaque, are a primary cause of oral diseases including caries, gingivitis, and periodontitis. Oral biofilms are ... ...

Abstract	Biofilms play an important role in the development and pathogenesis of many chronic infections. Oral biofilms, more commonly known as dental plaque, are a primary cause of oral diseases including caries, gingivitis, and periodontitis. Oral biofilms are commonly studied as model biofilm systems as they are easily accessible; thus, biofilm research in oral diseases is advanced with details of biofilm formation and bacterial interactions being well elucidated. In contrast, wound research has relatively recently directed attention to the role biofilms have in chronic wounds. This review discusses the biofilms in periodontal disease and chronic wounds with comparisons focusing on biofilm detection, biofilm formation, the immune response to biofilms, bacterial interaction, and quorum sensing. Current treatment modalities used by both fields and future therapies are also discussed.
MeSH term(s)	Bacteria/growth & development ; Biofilms/growth & development ; Chronic Disease ; Humans ; Mouth/microbiology ; Mouth Diseases/microbiology ; Quorum Sensing
Language	English
Publishing date	2013-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1174873-4
ISSN	1524-475X ; 1067-1927
ISSN (online)	1524-475X
ISSN	1067-1927
DOI	10.1111/wrr.12034
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Article ; Online: The formation of Streptococcus mutans persisters induced by the quorum-sensing peptide pheromone is affected by the LexA regulator.

Leung, Vincent / Ajdic, Dragana / Koyanagi, Stephanie / Lévesque, Céline M

Journal of bacteriology

2015 Volume 197, Issue 6, Page(s) 1083–1094

Abstract: The presence of multidrug-tolerant persister cells within microbial populations has been implicated in the resiliency of bacterial survival against antibiotic treatments and is a major contributing factor in chronic infections. The mechanisms by which ... ...

Abstract	The presence of multidrug-tolerant persister cells within microbial populations has been implicated in the resiliency of bacterial survival against antibiotic treatments and is a major contributing factor in chronic infections. The mechanisms by which these phenotypic variants are formed have been linked to stress response pathways in various bacterial species, but many of these mechanisms remain unclear. We have previously shown that in the cariogenic organism Streptococcus mutans, the quorum-sensing peptide CSP (competence-stimulating peptide) pheromone was a stress-inducible alarmone that triggered an increased formation of multidrug-tolerant persisters. In this study, we characterized SMU.2027, a CSP-inducible gene encoding a LexA ortholog. We showed that in addition to exogenous CSP exposure, stressors, including heat shock, oxidative stress, and ofloxacin antibiotic, were capable of triggering expression of lexA in an autoregulatory manner akin to that of LexA-like transcriptional regulators. We demonstrated the role of LexA and its importance in regulating tolerance toward DNA damage in a noncanonical SOS mechanism. We showed its involvement and regulatory role in the formation of persisters induced by the CSP-ComDE quorum-sensing regulatory system. We further identified key genes involved in sugar and amino acid metabolism, the clustered regularly interspaced short palindromic repeat (CRISPR) system, and autolysin from transcriptomic analyses that contribute to the formation of quorum-sensing-induced persister cells.
MeSH term(s)	Amino Acid Sequence ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Gene Expression Regulation, Bacterial/physiology ; Molecular Sequence Data ; Quorum Sensing/physiology ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism ; Streptococcus mutans/drug effects ; Streptococcus mutans/genetics ; Streptococcus mutans/metabolism ; Transcriptome
Chemical Substances	Bacterial Proteins ; LexA protein, Bacteria ; competence factor, Streptococcus ; Serine Endopeptidases (EC 3.4.21.-)
Language	English
Publishing date	2015-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/JB.02496-14
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Article ; Online: The Relationship of Bacterial Biofilms and Capsular Contracture in Breast Implants.

Ajdic, Dragana / Zoghbi, Yasmina / Gerth, David / Panthaki, Zubin J / Thaller, Seth

Aesthetic surgery journal

2016 Volume 36, Issue 3, Page(s) 297–309

Abstract: Capsular contracture is a common sequelae of implant-based breast augmentation. Despite its prevalence, the etiology of capsular contracture remains controversial. Numerous studies have identified microbial biofilms on various implantable materials, ... ...

Abstract	Capsular contracture is a common sequelae of implant-based breast augmentation. Despite its prevalence, the etiology of capsular contracture remains controversial. Numerous studies have identified microbial biofilms on various implantable materials, including breast implants. Furthermore, biofilms have been implicated in subclinical infections associated with other surgical implants. In this review, we discuss microbial biofilms as a potential etiology of capsular contracture. The review also outlines the key diagnostic modalities available to identify the possible infectious agents found in biofilm, as well as available preventative and treatment measures.
MeSH term(s)	Adult ; Animals ; Bacteria/growth & development ; Biofilms/growth & development ; Breast Implantation/adverse effects ; Breast Implants/adverse effects ; Female ; Host-Pathogen Interactions ; Humans ; Implant Capsular Contracture/diagnosis ; Implant Capsular Contracture/microbiology ; Implant Capsular Contracture/prevention & control ; Implant Capsular Contracture/therapy ; Prognosis ; Prosthesis-Related Infections/diagnosis ; Prosthesis-Related Infections/microbiology ; Prosthesis-Related Infections/prevention & control ; Prosthesis-Related Infections/therapy ; Risk Factors ; Young Adult
Language	English
Publishing date	2016-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2087022-X
ISSN	1527-330X ; 1090-820X ; 1084-0761
ISSN (online)	1527-330X
ISSN	1090-820X ; 1084-0761
DOI	10.1093/asj/sjv177
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Article ; Online: Role of the Streptococcus mutans irvA gene in GbpC-independent, dextran-dependent aggregation and biofilm formation.

Zhu, Min / Ajdić, Dragana / Liu, Yuan / Lynch, David / Merritt, Justin / Banas, Jeffrey A

Applied and environmental microbiology

2009 Volume 75, Issue 22, Page(s) 7037–7043

Abstract: Dextran-dependent aggregation (DDAG) of Streptococcus mutans is an in vitro phenomenon that is believed to represent a property of the organism that is beneficial for sucrose-dependent biofilm development. GbpC, a cell surface glucan-binding protein, is ... ...

Abstract	Dextran-dependent aggregation (DDAG) of Streptococcus mutans is an in vitro phenomenon that is believed to represent a property of the organism that is beneficial for sucrose-dependent biofilm development. GbpC, a cell surface glucan-binding protein, is responsible for DDAG in S. mutans when cultured under defined stressful conditions. Recent reports have described a putative transcriptional regulator gene, irvA, located just upstream of gbpC, that is normally repressed by the product of an adjacent gene, irvR. When repression of irvA is relieved, there is a resulting increase in the expression of GbpC and decreases in competence and synthesis of the antibiotic mutacin I. This study examined the role of irvA in DDAG and biofilm formation by engineering strains that overexpressed irvA (IrvA+) on an extrachromosomal plasmid. The IrvA+ strain displayed large aggregation particles that did not require stressful growth conditions. A novel finding was that overexpression of irvA in a gbpC mutant background retained a measure of DDAG, albeit very small aggregation particles. Biofilms formed by the IrvA+ strain in the parental background possessed larger-than-normal microcolonies. In a gbpC mutant background, the overexpression of irvA reversed the fragile biofilm phenotype normally associated with loss of GbpC. Real-time PCR and Northern blot analyses found that expression of gbpC did not change significantly in the IrvA+ strain but expression of spaP, encoding the major surface adhesin P1, increased significantly. Inactivation of spaP eliminated the small-particle DDAG. The results suggest that IrvA promotes DDAG not only by GbpC, but also via an increase in P1.
MeSH term(s)	Adhesins, Bacterial/metabolism ; Bacterial Adhesion/genetics ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Biofilms/growth & development ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Dextrans/metabolism ; Gene Expression Regulation, Bacterial ; Genes, Bacterial/genetics ; Lectins/genetics ; Lectins/metabolism ; Mutation ; Streptococcus mutans/genetics ; Streptococcus mutans/growth & development ; Streptococcus mutans/metabolism ; Streptococcus mutans/physiology
Chemical Substances	Adhesins, Bacterial ; Bacterial Proteins ; Carrier Proteins ; Dextrans ; Lectins ; glucan-binding proteins
Language	English
Publishing date	2009-09-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	223011-2
ISSN	1098-5336 ; 0099-2240
ISSN (online)	1098-5336
ISSN	0099-2240
DOI	10.1128/AEM.01015-09
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Article: The Formation of Streptococcus mutans Persisters Induced by the Quorum-Sensing Peptide Pheromone Is Affected by the LexA Regulator

Leung, Vincent / Ajdic, Dragana / Koyanagi, Stephanie / Léévesque, Céline M

Journal of bacteriology. 2015 Mar. 15, v. 197, no. 6

2015

Abstract	The presence of multidrug-tolerant persister cells within microbial populations has been implicated in the resiliency of bacterial survival against antibiotic treatments and is a major contributing factor in chronic infections. The mechanisms by which these phenotypic variants are formed have been linked to stress response pathways in various bacterial species, but many of these mechanisms remain unclear. We have previously shown that in the cariogenic organism Streptococcus mutans , the quorum-sensing peptide CSP (competence-stimulating peptide) pheromone was a stress-inducible alarmone that triggered an increased formation of multidrug-tolerant persisters. In this study, we characterized SMU.2027, a CSP-inducible gene encoding a LexA ortholog. We showed that in addition to exogenous CSP exposure, stressors, including heat shock, oxidative stress, and ofloxacin antibiotic, were capable of triggering expression of lexA in an autoregulatory manner akin to that of LexA-like transcriptional regulators. We demonstrated the role of LexA and its importance in regulating tolerance toward DNA damage in a noncanonical SOS mechanism. We showed its involvement and regulatory role in the formation of persisters induced by the CSP-ComDE quorum-sensing regulatory system. We further identified key genes involved in sugar and amino acid metabolism, the clustered regularly interspaced short palindromic repeat (CRISPR) system, and autolysin from transcriptomic analyses that contribute to the formation of quorum-sensing-induced persister cells.
Keywords	DNA damage ; Streptococcus mutans ; amino acid metabolism ; antibiotics ; gametolysin ; genes ; heat shock response ; ofloxacin ; oxidative stress ; pheromones ; quorum sensing ; transcription factors ; transcriptomics
Language	English
Dates of publication	2015-0315
Size	p. 1083-1094.
Publishing place	American Society for Microbiology
Document type	Article
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/JB.02496-14
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Article: Comparative genomics of streptococcal species.

Ferretti, Joseph J / Ajdic, Dragana / McShan, W Michael

The Indian journal of medical research

2004 Volume 119 Suppl, Page(s) 1–6

Abstract: Microbial genome sequencing has produced an unprecedented amount of new information and insights into an organism's metabolic activities, virulence properties, and evolution. The complete genome sequence has been reported for four different species of ... ...

Abstract	Microbial genome sequencing has produced an unprecedented amount of new information and insights into an organism's metabolic activities, virulence properties, and evolution. The complete genome sequence has been reported for four different species of streptococci, including Streptococcus pyogenes, S. agalactiae, S. pneumoniae and S. mutans. Comparative genome analysis among organisms of the same species not only shows a high degree of similarity in gene content and organization, but also a high degree of sequence heterogeneity as evidenced by the large number of single nucleotide polymorphisms present. Considerable differences were also observed in the number of mobile genetic elements found in each organism, including complete and partial bacteriophage genomes, IS elements, transposons, and plasmids. S. pyogenes was the only species to contain complete bacteriophage genomes in its genome, while only S. pneumoniae and S. mutans contained the full complement of competence genes essential for natural transformation. Comparative genome analysis between the species showed that S. pyogenes was more closely related to S. agalactiae than with S. pneumoniae or S. mutans.
MeSH term(s)	Genome, Bacterial ; Species Specificity ; Streptococcus/genetics
Language	English
Publishing date	2004-05
Publishing country	India
Document type	Comparative Study ; Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	390883-5
ISSN	0971-5916 ; 0019-5340
ISSN	0971-5916 ; 0019-5340
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