scholarly journals Why do plasmids manipulate the expression of bacterial phenotypes?

2021 ◽  
Vol 377 (1842) ◽  
Author(s):  
Kathryn Billane ◽  
Ellie Harrison ◽  
Duncan Cameron ◽  
Michael A. Brockhurst
Keyword(s):  
Side Effects ◽  
Host Cell ◽  
Vertical Transmission ◽  
Horizontal Transmission ◽  
Host Cells ◽  
Gene Exchange ◽  
Theme Issue ◽  
Adaptive Traits ◽  
Evolutionary Role ◽  
Plasmid Conjugation

Conjugative plasmids play an important role in bacterial evolution by transferring niche-adaptive traits between lineages, thus driving adaptation and genome diversification. It is increasingly clear, however, that in addition to this evolutionary role, plasmids also manipulate the expression of a broad range of bacterial phenotypes. In this review, we argue that the effects that plasmids have on the expression of bacterial phenotypes may often represent plasmid adaptations, rather than mere deleterious side effects. We begin by summarizing findings from untargeted omics analyses, which give a picture of the global effects of plasmid acquisition on host cells. Thereafter, because many plasmids are capable of both vertical and horizontal transmission, we distinguish plasmid-mediated phenotypic effects into two main classes based upon their potential fitness benefit to plasmids: (i) those that promote the competitiveness of the host cell in a given niche and thereby increase plasmid vertical transmission, and (ii) those that promote plasmid conjugation and thereby increase plasmid horizontal transmission. Far from being mere vehicles for gene exchange, we propose that plasmids often act as sophisticated genetic parasites capable of manipulating their bacterial hosts for their own benefit. This article is part of the theme issue ‘The secret lives of microbial mobile genetic elements’.

scholarly journals The dilution effect limits plasmid horizontal transmission in multispecies bacterial communities

Microbiology ◽  
2021 ◽  
Vol 167 (9) ◽  
Author(s):  
Anastasia Kottara ◽  
Laura Carrilero ◽  
Ellie Harrison ◽  
James P. J. Hall ◽  
Michael A. Brockhurst
Keyword(s):  
Host Species ◽  
Bacterial Communities ◽  
Horizontal Transmission ◽  
Dilution Effect ◽  
Infection Risk ◽  
Host Cells ◽  
Evolutionary Innovation ◽  
Genomic Divergence ◽  
Plasmid Diversity ◽  
Plasmid Conjugation

By transferring ecologically important traits between species, plasmids drive genomic divergence and evolutionary innovation in their bacterial hosts. Bacterial communities are often diverse and contain multiple coexisting plasmids, but the dynamics of plasmids in multi-species communities are poorly understood. Here, we show, using experimental multi-species communities containing two plasmids, that bacterial diversity limits the horizontal transmission of plasmids due to the ‘dilution effect’; this is an epidemiological phenomenon whereby living alongside less proficient host species reduces the expected infection risk for a focal host species. In addition, plasmid horizontal transmission was also affected by plasmid diversity, such that the rate of plasmid conjugation was reduced from co-infected host cells carrying both plasmids. In diverse microbial communities, plasmid spread may be limited by the dilution effect and plasmid–plasmid interactions, reducing the rate of horizontal transmission.

scholarly journals Characterization and Growth of Polymorphic Rickettsia felis in a Tick Cell Line

2008 ◽  
Vol 74 (10) ◽  
pp. 3151-3158 ◽  
Author(s):  
Piyanate Sunyakumthorn ◽  
Apichai Bourchookarn ◽  
Walairat Pornwiroon ◽  
Connie David ◽  
Steven A. Barker ◽  
...  
Keyword(s):  
Host Cell ◽  
Short Form ◽  
Horizontal Transmission ◽  
Pcr Amplification ◽  
Host Cells ◽  
In Vitro Assays ◽  
Rickettsia Felis ◽  
Transmission Potential ◽  
Long Form

ABSTRACT Morphological differentiation in some arthropod-borne bacteria is correlated with increased bacterial virulence, transmission potential, and/or as a response to environmental stress. In the current study, we utilized an in vitro model to examine Rickettsia felis morphology and growth under various culture conditions and bacterial densities to identify potential factors that contribute to polymorphism in rickettsiae. We utilized microscopy (electron microscopy and immunofluorescence), genomic (PCR amplification and DNA sequencing of rickettsial genes), and proteomic (Western blotting and liquid chromatography-tandem mass spectrometry) techniques to identify and characterize morphologically distinct, long-form R. felis. Without exchange of host cell growth medium, polymorphic R. felis was detected at 12 days postinoculation when rickettsiae were seeded at a multiplicity of infection (MOI) of 5 and 50. Compared to short-form R. felis organisms, no change in membrane ultrastructure in long-form polymorphic rickettsiae was observed, and rickettsiae were up to six times the length of typical short-form rickettsiae. In vitro assays demonstrated that short-form R. felis entered into and replicated in host cells faster than long-form R. felis. However, when both short- and long-form R. felis organisms were maintained in cell-free medium for 12 days, the infectivity of short-form R. felis was decreased compared to long-form R. felis organisms, which were capable of entering host cells, suggesting that long-form R. felis is more stable outside the host cell. The relationship between rickettsial polymorphism and rickettsial survivorship should be examined further as the yet undetermined route of horizontal transmission of R. felis may utilize metabolically and morphologically distinct forms for successful transmission.

scholarly journals The dilution effect limits plasmid horizontal transmission in multispecies bacterial communities

2021 ◽  
Author(s):  
Anastasia Kottara ◽  
Laura Carrilero ◽  
Ellie Harrison ◽  
James Peter John Hall ◽  
Michael Brockhurst
Keyword(s):  
Host Species ◽  
Bacterial Communities ◽  
Horizontal Transmission ◽  
Dilution Effect ◽  
Infection Risk ◽  
Host Cells ◽  
Evolutionary Innovation ◽  
Genomic Divergence ◽  
Plasmid Diversity ◽  
Plasmid Conjugation

By transferring ecologically important traits between species, plasmids drive genomic divergence and evolutionary innovation in their bacterial hosts. Bacterial communities are often diverse and contain multiple coexisting plasmids, but the dynamics of plasmids in multispecies communities are poorly understood. Here, we show, using experimental multispecies communities containing two plasmids, that bacterial diversity limits the horizontal transmission of plasmids due to the dilution effect; an epidemiological phenomenon whereby living alongside less proficient host species reduces the expected infection risk for a focal host species. In addition, plasmid horizontal transmission was also affected by plasmid diversity, such that the rate of plasmid conjugation was reduced from coinfected host cells carrying both plasmids. In diverse microbial communities, plasmid spread may be limited by the dilution effect and plasmid-plasmid interactions reducing the rate of horizontal transmission.

SARS-CoV-2 Biology Insights, Part I. Genome-wide structure and druggability: literature review (Preprint)

2020 ◽  
Author(s):  
Laura Lafon-Hughes
Keyword(s):  
Side Effects ◽  
Literature Review ◽  
Host Cell ◽  
Nucleoside Analogs ◽  
Viral Proteins ◽  
Therapeutic Strategies ◽  
Adverse Side Effects ◽  
Viral Proteases ◽  
Genome Wide ◽  
Therapeutic Alternatives

BACKGROUND COVID-19 pandemic prompts the study of coronavirus biology and search of putative therapeutic strategies. OBJECTIVE To compare SARS-CoV-2 genome-wide structure and proteins with other coronaviruses, focusing on putative coronavirus-specific or SARS-CoV-2 specific therapeutic designs. METHODS The genome-wide structure of SARS-CoV-2 was compared to that of SARS and other coronaviruses in order to gain insights, doing a literature review through Google searches. RESULTS There are promising therapeutic alternatives. Host cell targets could be modulated to hamper viral replication, but targeting viral proteins directly would be a better therapeutic design, since fewer adverse side effects would be expected. CONCLUSIONS Therapeutic strategies (Figure 1) could include the modulation of host targets (PARPs, kinases) , competition with G-quadruplexes or nucleoside analogs to hamper RDRP. The nicest anti-CoV options include inhibitors of the conserved essential viral proteases and drugs that interfere ribosome slippage at the -1 PRF site.

scholarly journals Metabolic Signatures of Cryptosporidium parvum-Infected HCT-8 Cells and Impact of Selected Metabolic Inhibitors on C. parvum Infection under Physioxia and Hyperoxia

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 60
Author(s):  
Juan Vélez ◽  
Zahady Velasquez ◽  
Liliana M. R. Silva ◽  
Ulrich Gärtner ◽  
Klaus Failing ◽  
...  
Keyword(s):  
Host Cell ◽  
Cryptosporidium Parvum ◽  
Cell Metabolism ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Host Cells ◽  
Metabolic Inhibitors ◽  
Low Oxygen ◽  
Metabolic Signatures

Cryptosporidium parvum is an apicomplexan zoonotic parasite recognized as the second leading-cause of diarrhoea-induced mortality in children. In contrast to other apicomplexans, C.parvum has minimalistic metabolic capacities which are almost exclusively based on glycolysis. Consequently, C. parvum is highly dependent on its host cell metabolism. In vivo (within the intestine) infected epithelial host cells are typically exposed to low oxygen pressure (1–11% O2, termed physioxia). Here, we comparatively analyzed the metabolic signatures of C. parvum-infected HCT-8 cells cultured under both, hyperoxia (21% O2), representing the standard oxygen condition used in most experimental settings, and physioxia (5% O2), to be closer to the in vivo situation. The most pronounced effect of C. parvum infection on host cell metabolism was, on one side, an increase in glucose and glutamine uptake, and on the other side, an increase in lactate release. When cultured in a glutamine-deficient medium, C. parvum infection led to a massive increase in glucose consumption and lactate production. Together, these results point to the important role of both glycolysis and glutaminolysis during C. parvum intracellular replication. Referring to obtained metabolic signatures, we targeted glycolysis as well as glutaminolysis in C. parvum-infected host cells by using the inhibitors lonidamine [inhibitor of hexokinase, mitochondrial carrier protein (MCP) and monocarboxylate transporters (MCT) 1, 2, 4], galloflavin (lactate dehydrogenase inhibitor), syrosingopine (MCT1- and MCT4 inhibitor) and compound 968 (glutaminase inhibitor) under hyperoxic and physioxic conditions. In line with metabolic signatures, all inhibitors significantly reduced parasite replication under both oxygen conditions, thereby proving both energy-related metabolic pathways, glycolysis and glutaminolysis, but also lactate export mechanisms via MCTs as pivotal for C. parvum under in vivo physioxic conditions of mammals.

scholarly journals The Campylobacter jejuni CiaD effector co-opts the host cell protein IQGAP1 to promote cell entry

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nicholas M. Negretti ◽  
Christopher R. Gourley ◽  
Prabhat K. Talukdar ◽  
Geremy Clair ◽  
Courtney M. Klappenbach ◽  
...  
Keyword(s):  
Host Cell ◽  
Campylobacter Jejuni ◽  
Foodborne Pathogen ◽  
Small Gtpase ◽  
Host Cells ◽  
Cell Protein ◽  
Host Cell Protein ◽  
Cell Binding ◽  
Actin Reorganization ◽  
Cell Cytosol

AbstractCampylobacter jejuni is a foodborne pathogen that binds to and invades the epithelial cells lining the human intestinal tract. Maximal invasion of host cells by C. jejuni requires cell binding as well as delivery of the Cia proteins (Campylobacter invasion antigens) to the host cell cytosol via the flagellum. Here, we show that CiaD binds to the host cell protein IQGAP1 (a Ras GTPase-activating-like protein), thus displacing RacGAP1 from the IQGAP1 complex. This, in turn, leads to the unconstrained activity of the small GTPase Rac1, which is known to have roles in actin reorganization and internalization of C. jejuni. Our results represent the identification of a host cell protein targeted by a flagellar secreted effector protein and demonstrate that C. jejuni-stimulated Rac signaling is dependent on IQGAP1.

scholarly journals A Single-Pass Type I Membrane Protein from the Apicomplexan Parasite Cryptosporidium parvum with Nanomolar Binding Affinity to Host Cell Surface

2021 ◽  
Vol 9 (5) ◽  
pp. 1015
Author(s):  
Tianyu Zhang ◽  
Xin Gao ◽  
Dongqiang Wang ◽  
Jixue Zhao ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Cell Surface ◽  
Host Cell ◽  
Binding Affinity ◽  
Cryptosporidium Parvum ◽  
Host Cells ◽  
Watery Diarrhea ◽  
Type I ◽  
Single Pass ◽  
Host Cell Surface

Cryptosporidium parvum is a globally recognized zoonotic parasite of medical and veterinary importance. This parasite mainly infects intestinal epithelial cells and causes mild to severe watery diarrhea that could be deadly in patients with weakened or defect immunity. However, its molecular interactions with hosts and pathogenesis, an important part in adaptation of parasitic lifestyle, remain poorly understood. Here we report the identification and characterization of a C. parvum T-cell immunomodulatory protein homolog (CpTIPH). CpTIPH is a 901-aa single-pass type I membrane protein encoded by cgd5_830 gene that also contains a short Vibrio, Colwellia, Bradyrhizobium and Shewanella (VCBS) repeat and relatively long integrin alpha (ITGA) N-terminus domain. Immunofluorescence assay confirmed the location of CpTIPH on the cell surface of C. parvum sporozoites. In congruence with the presence of VCBS repeat and ITGA domain, CpTIPH displayed high, nanomolar binding affinity to host cell surface (i.e., Kd(App) at 16.2 to 44.7 nM on fixed HCT-8 and CHO-K1 cells, respectively). The involvement of CpTIPH in the parasite invasion is partly supported by experiments showing that an anti-CpTIPH antibody could partially block the invasion of C. parvum sporozoites into host cells. These observations provide a strong basis for further investigation of the roles of CpTIPH in parasite-host cell interactions.

scholarly journals Revisiting Ehrlichia ruminantium Replication Cycle Using Proteomics: The Host and the Bacterium Perspectives

2021 ◽  
Vol 9 (6) ◽  
pp. 1144
Author(s):  
Isabel Marcelino ◽  
Philippe Holzmuller ◽  
Ana Coelho ◽  
Gabriel Mazzucchelli ◽  
Bernard Fernandez ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Host Cell ◽  
Cell Metabolism ◽  
Replication Cycle ◽  
Host Cells ◽  
Ehrlichia Ruminantium ◽  
Host Interaction ◽  
Infected Cells ◽  
Related Proteins

The Rickettsiales Ehrlichia ruminantium, the causal agent of the fatal tick-borne disease Heartwater, induces severe damage to the vascular endothelium in ruminants. Nevertheless, E. ruminantium-induced pathobiology remains largely unknown. Our work paves the way for understanding this phenomenon by using quantitative proteomic analyses (2D-DIGE-MS/MS, 1DE-nanoLC-MS/MS and biotin-nanoUPLC-MS/MS) of host bovine aorta endothelial cells (BAE) during the in vitro bacterium intracellular replication cycle. We detect 265 bacterial proteins (including virulence factors), at all time-points of the E. ruminantium replication cycle, highlighting a dynamic bacterium–host interaction. We show that E. ruminantium infection modulates the expression of 433 host proteins: 98 being over-expressed, 161 under-expressed, 140 detected only in infected BAE cells and 34 exclusively detected in non-infected cells. Cystoscape integrated data analysis shows that these proteins lead to major changes in host cell immune responses, host cell metabolism and vesicle trafficking, with a clear involvement of inflammation-related proteins in this process. Our findings led to the first model of E. ruminantium infection in host cells in vitro, and we highlight potential biomarkers of E. ruminantium infection in endothelial cells (such as ROCK1, TMEM16K, Albumin and PTPN1), which may be important to further combat Heartwater, namely by developing non-antibiotic-based strategies.

scholarly journals The Importance of Therapeutically Targeting the Binary Toxin from Clostridioides difficile

2021 ◽  
Vol 22 (6) ◽  
pp. 2926
Author(s):  
Dinendra L. Abeyawardhane ◽  
Raquel Godoy-Ruiz ◽  
Kaylin A. Adipietro ◽  
Kristen M. Varney ◽  
Richard R. Rustandi ◽  
...  
Keyword(s):  
Host Cell ◽  
The Elderly ◽  
Cell Receptor ◽  
Host Cells ◽  
Binary Toxin ◽  
Clostridioides Difficile ◽  
Host Cell Receptor ◽  
Oligomeric Assembly ◽  
Nosocomial Disease ◽  
Binary Toxins

Novel therapeutics are needed to treat pathologies associated with the Clostridioides difficile binary toxin (CDT), particularly when C. difficile infection (CDI) occurs in the elderly or in hospitalized patients having illnesses, in addition to CDI, such as cancer. While therapies are available to block toxicities associated with the large clostridial toxins (TcdA and TcdB) in this nosocomial disease, nothing is available yet to treat toxicities arising from strains of CDI having the binary toxin. Like other binary toxins, the active CDTa catalytic subunit of CDT is delivered into host cells together with an oligomeric assembly of CDTb subunits via host cell receptor-mediated endocytosis. Once CDT arrives in the host cell’s cytoplasm, CDTa catalyzes the ADP-ribosylation of G-actin leading to degradation of the cytoskeleton and rapid cell death. Although a detailed molecular mechanism for CDT entry and host cell toxicity is not yet fully established, structural and functional resemblances to other binary toxins are described. Additionally, unique conformational assemblies of individual CDT components are highlighted herein to refine our mechanistic understanding of this deadly toxin as is needed to develop effective new therapeutic strategies for treating some of the most hypervirulent and lethal strains of CDT-containing strains of CDI.

scholarly journals Pathogen induced subversion of NAD+ metabolism mediating host cell death: a target for development of chemotherapeutics

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ayushi Chaurasiya ◽  
Swati Garg ◽  
Ashish Khanna ◽  
Chintam Narayana ◽  
Ved Prakash Dwivedi ◽  
...  
Keyword(s):  
Cell Death ◽  
Host Cell ◽  
Nicotinamide Adenine Dinucleotide ◽  
Malaria Parasite ◽  
Host Cells ◽  
Nicotinamide Adenine ◽  
Targeted Therapeutics ◽  
Nad Metabolism ◽  
Host Cell Death ◽  
Nanomolar Range

AbstractHijacking of host metabolic status by a pathogen for its regulated dissemination from the host is prerequisite for the propagation of infection. M. tuberculosis secretes an NAD+-glycohydrolase, TNT, to induce host necroptosis by hydrolyzing Nicotinamide adenine dinucleotide (NAD+). Herein, we expressed TNT in macrophages and erythrocytes; the host cells for M. tuberculosis and the malaria parasite respectively, and found that it reduced the NAD+ levels and thereby induced necroptosis and eryptosis resulting in premature dissemination of pathogen. Targeting TNT in M. tuberculosis or induced eryptosis in malaria parasite interferes with pathogen dissemination and reduction in the propagation of infection. Building upon our discovery that inhibition of pathogen-mediated host NAD+ modulation is a way forward for regulation of infection, we synthesized and screened some novel compounds that showed inhibition of NAD+-glycohydrolase activity and pathogen infection in the nanomolar range. Overall this study highlights the fundamental importance of pathogen-mediated modulation of host NAD+ homeostasis for its infection propagation and novel inhibitors as leads for host-targeted therapeutics.

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