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Article ; Online: Diversity of Contact-Dependent Growth Inhibition Systems of

Allen, Jonathan P / Hauser, Alan R

2019 Volume 201, Issue 14

Abstract: Contact-dependent growth inhibition (CDI) systems are used in bacterial competition to hinder the growth of neighboring microbes. These systems utilize a two-partner secretion mechanism to display the CdiA exoprotein at the bacterial cell surface. CdiA ... ...

Abstract	Contact-dependent growth inhibition (CDI) systems are used in bacterial competition to hinder the growth of neighboring microbes. These systems utilize a two-partner secretion mechanism to display the CdiA exoprotein at the bacterial cell surface. CdiA forms a long filamentous stalk that facilitates binding to a target cell and delivery of a C-terminal toxin (CT) domain. This CT domain is processed and delivered into the cytoplasm of a target cell upon contact. CDI systems also encode a cognate immunity protein (CdiI) that protects siblings and resistant targeted cells from intoxication by high-affinity binding to the CT. CdiA CT domains vary among strains within a species, and many alleles encode enzymatic functions that target nucleic acids. This variation is thought to help drive diversity and adaptation within a species. CdiA diversity is well studied in
MeSH term(s)	Alleles ; Bacterial Proteins/genetics ; Bacterial Proteins/physiology ; Bacterial Toxins/metabolism ; Escherichia coli ; Escherichia coli Proteins ; Membrane Proteins/genetics ; Membrane Proteins/physiology ; Microbial Interactions ; Pseudomonas aeruginosa/genetics ; Pseudomonas aeruginosa/growth & development
Chemical Substances	Bacterial Proteins ; Bacterial Toxins ; CdiA protein, E coli ; Escherichia coli Proteins ; Membrane Proteins
Language	English
Publishing date	2019-06-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/JB.00776-18
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Book: Technology and inequality

Allen, Jonathan P

concentrated wealth in a digital world

(Palgrave Pivot)

2017

Author's details	Jonathan P. Allen
Series title	Palgrave Pivot
Keywords	Technischer Fortschritt ; Soziale Ungleichheit ; Informationstechnik ; Social Web ; Share Economy ; E-Business
Language	English
Size	xi, 158 Seiten, Illustrationen, 21 cm x 14.8 cm
Document type	Book
ISBN	3319569570 ; 9783319569574 ; 9783319569581 ; 3319569589
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Article ; Online: Forest and Trees: Exploring Bacterial Virulence with Genome-wide Association Studies and Machine Learning.

Allen, Jonathan P / Snitkin, Evan / Pincus, Nathan B / Hauser, Alan R

Trends in microbiology

2021 Volume 29, Issue 7, Page(s) 621–633

Abstract: The advent of inexpensive and rapid sequencing technologies has allowed bacterial whole-genome sequences to be generated at an unprecedented pace. This wealth of information has revealed an unanticipated degree of strain-to-strain genetic diversity ... ...

Abstract	The advent of inexpensive and rapid sequencing technologies has allowed bacterial whole-genome sequences to be generated at an unprecedented pace. This wealth of information has revealed an unanticipated degree of strain-to-strain genetic diversity within many bacterial species. Awareness of this genetic heterogeneity has corresponded with a greater appreciation of intraspecies variation in virulence. A number of comparative genomic strategies have been developed to link these genotypic and pathogenic differences with the aim of discovering novel virulence factors. Here, we review recent advances in comparative genomic approaches to identify bacterial virulence determinants, with a focus on genome-wide association studies and machine learning.
MeSH term(s)	Bacteria/classification ; Bacteria/genetics ; Bacteria/pathogenicity ; Genetic Variation ; Genome, Bacterial ; Genome-Wide Association Study/methods ; Genomics ; Genotype ; Machine Learning ; Phylogeny ; Virulence/genetics ; Virulence Factors/genetics
Chemical Substances	Virulence Factors
Language	English
Publishing date	2021-01-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1158963-2
ISSN	1878-4380 ; 0966-842X
ISSN (online)	1878-4380
ISSN	0966-842X
DOI	10.1016/j.tim.2020.12.002
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Article: Forest and Trees: Exploring Bacterial Virulence with Genome-wide Association Studies and Machine Learning

Allen, Jonathan P / Snitkin, Evan / Pincus, Nathan B / Hauser, Alan R

Trends in microbiology. 2021 July, v. 29, no. 7

2021

Abstract	The advent of inexpensive and rapid sequencing technologies has allowed bacterial whole-genome sequences to be generated at an unprecedented pace. This wealth of information has revealed an unanticipated degree of strain-to-strain genetic diversity within many bacterial species. Awareness of this genetic heterogeneity has corresponded with a greater appreciation of intraspecies variation in virulence. A number of comparative genomic strategies have been developed to link these genotypic and pathogenic differences with the aim of discovering novel virulence factors. Here, we review recent advances in comparative genomic approaches to identify bacterial virulence determinants, with a focus on genome-wide association studies and machine learning.
Keywords	forests ; genetic heterogeneity ; genomics ; microbiology ; virulence
Language	English
Dates of publication	2021-07
Size	p. 621-633.
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	1158963-2
ISSN	1878-4380 ; 0966-842X
ISSN (online)	1878-4380
ISSN	0966-842X
DOI	10.1016/j.tim.2020.12.002
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Article ; Online: Systemic infection facilitates transmission of Pseudomonas aeruginosa in mice.

Bachta, Kelly E R / Allen, Jonathan P / Cheung, Bettina H / Chiu, Cheng-Hsun / Hauser, Alan R

Nature communications

2020 Volume 11, Issue 1, Page(s) 543

Abstract: Health care-associated infections such as Pseudomonas aeruginosa bacteremia pose a major clinical risk for hospitalized patients. However, these systemic infections are presumed to be a "dead-end" for P. aeruginosa and to have no impact on transmission. ... ...

Abstract	Health care-associated infections such as Pseudomonas aeruginosa bacteremia pose a major clinical risk for hospitalized patients. However, these systemic infections are presumed to be a "dead-end" for P. aeruginosa and to have no impact on transmission. Here, we use a mouse infection model to show that P. aeruginosa can spread from the bloodstream to the gallbladder, where it replicates to extremely high numbers. Bacteria in the gallbladder can then seed the intestines and feces, leading to transmission to uninfected cage-mate mice. Our work shows that the gallbladder is crucial for spread of P. aeruginosa from the bloodstream to the feces during bacteremia, a process that promotes transmission in this experimental system. Further research is needed to test to what extent these findings are relevant to infections in patients.
MeSH term(s)	Animals ; Bacteremia/microbiology ; Bacteremia/pathology ; Bacteremia/transmission ; Disease Models, Animal ; Epithelium/microbiology ; Feces/microbiology ; Female ; Gallbladder/microbiology ; Gallbladder/pathology ; Gastrointestinal Tract/microbiology ; Gastrointestinal Tract/pathology ; Humans ; Intestines/microbiology ; Intestines/pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Pneumonia/microbiology ; Pseudomonas Infections/microbiology ; Pseudomonas Infections/pathology ; Pseudomonas Infections/transmission ; Pseudomonas aeruginosa/pathogenicity ; Type III Secretion Systems
Chemical Substances	Type III Secretion Systems
Keywords	covid19
Language	English
Publishing date	2020-01-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-020-14363-4
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Article ; Online: CpsY influences Streptococcus iniae cell wall adaptations important for neutrophil intracellular survival.

Allen, Jonathan P / Neely, Melody N

Infection and immunity

2012 Volume 80, Issue 5, Page(s) 1707–1715

Abstract: The ability of a pathogen to evade neutrophil phagocytic killing mechanisms is critically important for dissemination and establishment of a systemic infection. Understanding how pathogens overcome these innate defenses is essential for the development ... ...

Abstract	The ability of a pathogen to evade neutrophil phagocytic killing mechanisms is critically important for dissemination and establishment of a systemic infection. Understanding how pathogens overcome these innate defenses is essential for the development of optimal therapeutic strategies for invasive infections. CpsY is a conserved transcriptional regulator previously identified as an important virulence determinant for systemic infection of Streptococcus iniae. While orthologs of CpsY have been associated with the regulation of methionine metabolism and uptake pathways, CpsY additionally functions in protection from neutrophil-mediated killing. S. iniae does not alter neutrophil phagosomal maturation but instead is able to adapt to the extreme bactericidal environment of a mature neutrophil phagosome, a property dependent upon CpsY. This CpsY-dependent adaptation appears to involve stabilization of the cell wall through peptidoglycan O-acetylation and repression of cellular autolysins. Furthermore, S. iniae continues to be a powerful model for investigation of bacterial adaptations during systemic streptococcal infection.
MeSH term(s)	Adaptation, Physiological/physiology ; Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Cell Wall/metabolism ; Drug Resistance, Bacterial ; Gene Expression Regulation, Bacterial/physiology ; Mutation ; Neutrophils/microbiology ; Phagosomes ; Promoter Regions, Genetic ; Streptococcus/drug effects ; Streptococcus/physiology ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Anti-Bacterial Agents ; Bacterial Proteins ; Transcription Factors
Language	English
Publishing date	2012-02-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/IAI.00027-12
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Article ; Online: A comparative genomics approach identifies contact-dependent growth inhibition as a virulence determinant.

Allen, Jonathan P / Ozer, Egon A / Minasov, George / Shuvalova, Ludmilla / Kiryukhina, Olga / Satchell, Karla J F / Hauser, Alan R

Proceedings of the National Academy of Sciences of the United States of America

2020 Volume 117, Issue 12, Page(s) 6811–6821

Abstract: Emerging evidence suggests ... ...

Abstract	Emerging evidence suggests the
MeSH term(s)	Animals ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Bacterial Toxins/genetics ; Bacterial Toxins/metabolism ; Contact Inhibition/genetics ; Escherichia coli/genetics ; Escherichia coli/growth & development ; Escherichia coli/isolation & purification ; Escherichia coli/metabolism ; Escherichia coli Infections/microbiology ; Female ; Genome, Bacterial ; Genomics/methods ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Pseudomonas Infections/microbiology ; Pseudomonas aeruginosa/genetics ; Pseudomonas aeruginosa/growth & development ; Pseudomonas aeruginosa/isolation & purification ; Pseudomonas aeruginosa/metabolism ; Signal Transduction ; Virulence ; Virulence Factors/genetics ; Virulence Factors/metabolism
Chemical Substances	Bacterial Proteins ; Bacterial Toxins ; Virulence Factors
Language	English
Publishing date	2020-03-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1919198117
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Zs.A 1148: Show issues

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Article ; Online: The Streptococcus iniae transcriptional regulator CpsY is required for protection from neutrophil-mediated killing and proper growth in vitro.

Allen, Jonathan P / Neely, Melody N

Infection and immunity

2011 Volume 79, Issue 11, Page(s) 4638–4648

Abstract: The ability of a pathogen to metabolically adapt to the local environment for optimal expression of virulence determinants is a continued area of research. Orthologs of the Streptococcus iniae LysR family regulator CpsY have been shown to regulate ... ...

Abstract	The ability of a pathogen to metabolically adapt to the local environment for optimal expression of virulence determinants is a continued area of research. Orthologs of the Streptococcus iniae LysR family regulator CpsY have been shown to regulate methionine biosynthesis and uptake pathways but appear to influence expression of several virulence genes as well. An S. iniae mutant with an in-frame deletion of cpsY (ΔcpsY mutant) is highly attenuated in a zebrafish infection model. The ΔcpsY mutant displays a methionine-independent growth defect in serum, which differs from the methionine-dependent defect observed for orthologous mutants of Streptococcus mutans and Streptococcus agalactiae. On the contrary, the ΔcpsY mutant can grow in excess of the wild type (WT) when supplemented with proteose peptone, suggesting an inability to properly regulate growth. CpsY is critical for protection of S. iniae from clearance by neutrophils in whole blood but is dispensable for intracellular survival in macrophages. Susceptibility of the ΔcpsY mutant to killing in whole blood is not due to a growth defect, because inhibition of neutrophil phagocytosis rescues the mutant to WT levels. Thus, CpsY appears to have a pleiotropic regulatory role for S. iniae, integrating metabolism and virulence. Furthermore, S. iniae provides a unique model to investigate the paradigm of CpsY-dependent regulation during systemic streptococcal infection.
MeSH term(s)	Animals ; Bacterial Adhesion ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Base Sequence ; Cell Line ; Gene Expression Regulation, Bacterial/physiology ; Macrophages/microbiology ; Methionine/metabolism ; Mice ; Neutrophils/physiology ; Promoter Regions, Genetic ; Streptococcus/genetics ; Streptococcus/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Zebrafish
Chemical Substances	Bacterial Proteins ; Transcription Factors ; Methionine (AE28F7PNPL)
Language	English
Publishing date	2011-09-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/IAI.05567-11
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Article ; Online: Characterization of the core and accessory genomes of Pseudomonas aeruginosa using bioinformatic tools Spine and AGEnt.

Ozer, Egon A / Allen, Jonathan P / Hauser, Alan R

BMC genomics

2014 Volume 15, Page(s) 737

Abstract: Background: Pseudomonas aeruginosa is an important opportunistic pathogen responsible for many infections in hospitalized and immunocompromised patients. Previous reports estimated that approximately 10% of its 6.6 Mbp genome varies from strain to ... ...

Abstract	Background: Pseudomonas aeruginosa is an important opportunistic pathogen responsible for many infections in hospitalized and immunocompromised patients. Previous reports estimated that approximately 10% of its 6.6 Mbp genome varies from strain to strain and is therefore referred to as "accessory genome". Elements within the accessory genome of P. aeruginosa have been associated with differences in virulence and antibiotic resistance. As whole genome sequencing of bacterial strains becomes more widespread and cost-effective, methods to quickly and reliably identify accessory genomic elements in newly sequenced P. aeruginosa genomes will be needed. Results: We developed a bioinformatic method for identifying the accessory genome of P. aeruginosa. First, the core genome was determined based on sequence conserved among the completed genomes of twelve reference strains using Spine, a software program developed for this purpose. The core genome was 5.84 Mbp in size and contained 5,316 coding sequences. We then developed an in silico genome subtraction program named AGEnt to filter out core genomic sequences from P. aeruginosa whole genomes to identify accessory genomic sequences of these reference strains. This analysis determined that the accessory genome of P. aeruginosa ranged from 6.9-18.0% of the total genome, was enriched for genes associated with mobile elements, and was comprised of a majority of genes with unknown or unclear function. Using these genomes, we showed that AGEnt performed well compared to other publically available programs designed to detect accessory genomic elements. We then demonstrated the utility of the AGEnt program by applying it to the draft genomes of two previously unsequenced P. aeruginosa strains, PA99 and PA103. Conclusions: The P. aeruginosa genome is rich in accessory genetic material. The AGEnt program accurately identified the accessory genomes of newly sequenced P. aeruginosa strains, even when draft genomes were used. As P. aeruginosa genomes become available at an increasingly rapid pace, this program will be useful in cataloging the expanding accessory genome of this bacterium and in discerning correlations between phenotype and accessory genome makeup. The combination of Spine and AGEnt should be useful in defining the accessory genomes of other bacterial species as well.
MeSH term(s)	Base Sequence ; Computational Biology ; Evolution, Molecular ; Genome, Bacterial ; Molecular Sequence Annotation ; Phylogeny ; Pseudomonas aeruginosa/genetics ; Sequence Analysis, DNA ; Software
Language	English
Publishing date	2014-08-29
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1471-2164
ISSN (online)	1471-2164
DOI	10.1186/1471-2164-15-737
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Article ; Online: Different paths to pathogenesis.

Allen, Jonathan P / Ozer, Egon A / Hauser, Alan R

Trends in microbiology

2014 Volume 22, Issue 4, Page(s) 168–169

Abstract: In a recent issue of Cell Host & Microbe, Elsen and colleagues identify a novel hemolysin in a highly virulent Pseudomonas aeruginosa strain that lacks a type III secretion system. Their analysis provides another example of how individual strains of P. ... ...

Abstract	In a recent issue of Cell Host & Microbe, Elsen and colleagues identify a novel hemolysin in a highly virulent Pseudomonas aeruginosa strain that lacks a type III secretion system. Their analysis provides another example of how individual strains of P. aeruginosa utilize different virulence mechanisms to cause severe infections.
MeSH term(s)	Animals ; Hemorrhage/etiology ; Humans ; Lung/pathology ; Membrane Transport Proteins/metabolism ; Pneumonia, Bacterial/microbiology ; Pore Forming Cytotoxic Proteins/metabolism ; Pseudomonas aeruginosa/pathogenicity ; Pseudomonas aeruginosa/physiology
Chemical Substances	Membrane Transport Proteins ; Pore Forming Cytotoxic Proteins
Language	English
Publishing date	2014-03-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1158963-2
ISSN	1878-4380 ; 0966-842X
ISSN (online)	1878-4380
ISSN	0966-842X
DOI	10.1016/j.tim.2014.02.013
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