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PLoS Neglected Tropical Diseases Aug 2020Presently, the principal tools to combat malaria are restricted to killing the parasite in infected people and killing the mosquito vector to thwart transmission. While...
Presently, the principal tools to combat malaria are restricted to killing the parasite in infected people and killing the mosquito vector to thwart transmission. While successful, these approaches are losing effectiveness in view of parasite resistance to drugs and mosquito resistance to insecticides. Clearly, new approaches to fight this deadly disease need to be developed. Recently, one such approach-engineering mosquito resident bacteria to secrete anti-parasite compounds-has proven in the laboratory to be highly effective. However, implementation of this strategy requires approval from regulators as it involves introduction of recombinant bacteria into the field. A frequent argument by regulators is that if something unexpectedly goes wrong after release, there must be a recall mechanism. This report addresses this concern. Previously we have shown that a Serratia bacterium isolated from a mosquito ovary is able to spread through mosquito populations and is amenable to be engineered to secrete anti-plasmodial compounds. We have introduced a plasmid into this bacterium that carries a fluorescent protein gene and show that when cultured in the laboratory, the plasmid is completely lost in about 130 bacterial generations. Importantly, when these bacteria were introduced into mosquitoes, the bacteria were transmitted from one generation to the next, but the plasmid was lost after three mosquito generations, rendering the bacteria non-recombinant (wild type). Furthermore, no evidence was obtained for horizontal transfer of the plasmid to other bacteria either in culture or in the mosquito. Prior to release, it is imperative to demonstrate that the genes that thwart parasite development in the mosquito are safe to the environment. This report describes a methodology to safely achieve this goal, utilizing transient expression from a plasmid that is gradually lost, returning the bacterium to wild type status.
Topics: Animals; Anopheles; Bacteria; Biological Control Agents; Disease Transmission, Infectious; Female; Malaria; Male; Mosquito Vectors; Ovary; Plasmids; Serratia
PubMed: 32810151
DOI: 10.1371/journal.pntd.0008542 -
Nature Communications Sep 2022The genus Serratia has been studied for over a century and includes clinically-important and diverse environmental members. Despite this, there is a paucity of genomic...
The genus Serratia has been studied for over a century and includes clinically-important and diverse environmental members. Despite this, there is a paucity of genomic information across the genus and a robust whole genome-based phylogenetic framework is lacking. Here, we have assembled and analysed a representative set of 664 genomes from across the genus, including 215 historic isolates originally used in defining the genus. Phylogenomic analysis of the genus reveals a clearly-defined population structure which displays deep divisions and aligns with ecological niche, as well as striking congruence between historical biochemical phenotyping data and contemporary genomics data. We highlight the genomic, phenotypic and plasmid diversity of Serratia, and provide evidence of different patterns of gene flow across the genus. Our work provides a framework for understanding the emergence of clinical and other lineages of Serratia.
Topics: Genome, Bacterial; Genomics; Phylogeny; Plasmids; Serratia
PubMed: 36057639
DOI: 10.1038/s41467-022-32929-2 -
FEMS Microbiology Reviews Jul 2007Many bacteria use cell-cell communication to monitor their population density, synchronize their behaviour and socially interact. This communication results in a... (Review)
Review
Many bacteria use cell-cell communication to monitor their population density, synchronize their behaviour and socially interact. This communication results in a coordinated gene regulation and is generally called quorum sensing. In gram-negative bacteria, the most common quorum signal molecules are acylated homoserine lactones (AHLs), although other low-molecular-mass signalling molecules have been described such as Autoinducer-2 (AI-2). The phenotypes that are regulated in Serratia species by means of AHLs are remarkably diverse and of profound biological and ecological significance, and often interconnected with other global regulators. Furthermore, AHL- and AI-2-mediated systems (less profoundly studied) are continuously being discovered and explored in Serratia spp., many having interesting twists on the basic theme. Therefore, this review will highlight the current known quorum sensing systems in Serratia spp., including the important nosocomial pathogen Serratia marcescens.
Topics: 4-Butyrolactone; Bacterial Proteins; Biofilms; Gene Expression Regulation, Bacterial; Homoserine; Humans; Lactones; Quorum Sensing; Serratia; Serratia marcescens; Signal Transduction
PubMed: 17459113
DOI: 10.1111/j.1574-6976.2007.00071.x -
Transactions of the Royal Society of... Oct 2018Human infections with Serratia spp. are generally limited to Serratia marcescens and the Serratia liquefaciens complex. There is little data regarding the infections...
BACKGROUND
Human infections with Serratia spp. are generally limited to Serratia marcescens and the Serratia liquefaciens complex. There is little data regarding the infections caused by the remaining Serratia spp., as they are seldom isolated from clinical specimens.
METHODS
In this health care setting in Kathmandu, Nepal routine blood culture is performed on all febrile patients with a temperature >38°C or when there is clinical suspicion of bacteremia. During 2015 we atypically isolated and identified several Serratia spp. We extracted clinical data from these cases and performed whole genome sequencing on all isolates using a MiSeq system (Ilumina, San Diego, CA, USA).
RESULTS
Between June and November 2015, we identified eight patients with suspected bacteremia that produced a positive blood culture for Serratia spp., six Serratia rubidaea and five Serratia marcescens. The S. rubidaea were isolated from three neonates and were concentrated in the neonatal intensive care unit between June and July 2015. All patients were severely ill and one patient died. Whole genome sequencing confirmed that six Nepalese S. rubidaea sequences were identical and indicative of a single-source outbreak.
CONCLUSIONS
Despite extensive screening we were unable to identify the source of the outbreak, but the inferred timeline suggested that these atypical infections were associated with the aftermath of two massive earthquakes. We speculate that deficits in hygienic behavior, combined with a lack of standard infection control, in the post-earthquake emergency situation contributed to these unusual Serratia spp. outbreaks.
Topics: Cross Infection; Earthquakes; Humans; Infant, Newborn; Infant, Premature; Infection Control; Intensive Care Units, Neonatal; Microbial Sensitivity Tests; Nepal; Serratia; Serratia Infections; Serratia marcescens
PubMed: 30107587
DOI: 10.1093/trstmh/try077 -
International Journal of Molecular... Jun 2020The article reviews the discovery, properties and functional activities of new bacterial enzymes, proteases grimelysin (ECP 32) of and protealysin of , characterized by... (Review)
Review
The article reviews the discovery, properties and functional activities of new bacterial enzymes, proteases grimelysin (ECP 32) of and protealysin of , characterized by both a highly specific "actinase" activity and their ability to stimulate bacterial invasion. Grimelysin cleaves the only polypeptide bond Gly42-Val43 in actin. This bond is not cleaved by any other proteases and leads to a reversible loss of actin polymerization. Similar properties were characteristic for another bacterial protease, protealysin. These properties made grimelysin and protealysin a unique tool to study the functional properties of actin. Furthermore, bacteria and , producing grimelysin and protealysin, invade eukaryotic cells, and the recombinant expressing the grimelysin or protealysins gene become invasive. Participation of the cellular c-Src and RhoA/ROCK signaling pathways in the invasion of eukaryotic cells by was shown, and involvement of E-cadherin in the invasion has been suggested. Moreover, membrane vesicles produced by were found to contain grimelysin, penetrate into eukaryotic cells and increase the invasion of bacteria into eukaryotic cells. These data indicate that the protease is a virulence factor, and actin can be a target for the protease upon its translocation into the host cell.
Topics: Actins; Bacterial Proteins; Endopeptidases; Proteolysis; Serratia; Serratia Infections; Substrate Specificity; Virulence; Virulence Factors
PubMed: 32512842
DOI: 10.3390/ijms21114025 -
The American Journal of Case Reports Sep 2019BACKGROUND Liver abscesses remain difficult to diagnose and treat. Risk factors include diabetes mellitus, liver cirrhosis, and immunodeficiency. The majority are... (Review)
Review
BACKGROUND Liver abscesses remain difficult to diagnose and treat. Risk factors include diabetes mellitus, liver cirrhosis, and immunodeficiency. The majority are pyogenic, resulting from bacterial infection. Research identifies species in the Serratia genus as the cause of pyogenic liver abscesses in only 0.25% of cases and only 1 Serratia species in each case appears to have been identified. To the best of our knowledge, the present case report is the first to involve overlapping Serratia species in a single liver abscess infection that induced cardiomyopathy. CASE REPORT A 45-year-old woman presented to our Emergency Department (ED) for severe generalized weakness. Initial test results indicated a diagnosis of microcytic anemia, hypomagnesemia, hypokalemia, hypocalcemia, hyperglycemia, type 2 diabetes mellitus, and severe heart failure. A computed tomography scan showed a 10-cm rim-enhancing fluid collection in the right hepatic lobe. Fluid drained from the suspected abscess tested positive for Serratia marcescens and Streptococcus viridans. The patient was treated with ceftriaxone and metronidazole, which she tolerated well. The abscess decreased to less than 9.8 mm. Twenty-one weeks after discharge, the patient received a cholecystectomy. Fluid drained from the residual abscess cultured positive for a different Serratia species, S. odorifera. CONCLUSIONS Diabetes mellitus and acute cholecystitis were key factors in the initial infections and abscess. We also suspect this is a rare case of cardiomyopathy induced by a Serratia infection. The source of the Serratia odorifera is less certain, as it postdates placement of a percutaneous drain, raising the potential for a nosocomial infection but not precluding the possibility that both Serratia species were previously present.
Topics: Cardiomyopathies; Cholecystitis, Acute; Diabetes Mellitus, Type 2; Female; Humans; Liver Abscess, Pyogenic; Middle Aged; Serratia; Serratia Infections
PubMed: 31506419
DOI: 10.12659/AJCR.918152 -
Communications Biology Apr 2022ExbB and ExbD are cytoplasmic membrane proteins that associate with TonB to convey the energy of the proton-motive force to outer membrane receptors in Gram-negative...
ExbB and ExbD are cytoplasmic membrane proteins that associate with TonB to convey the energy of the proton-motive force to outer membrane receptors in Gram-negative bacteria for iron uptake. The opportunistic pathogen Serratia marcescens (Sm) possesses both TonB and a heme-specific TonB paralog, HasB. ExbB has a long periplasmic extension absent in other bacteria such as E. coli (Ec). Long ExbB's are found in several genera of Alphaproteobacteria, most often in correlation with a hasB gene. We investigated specificity determinants of ExbB and HasB. We determined the cryo-EM structures of ExbB and of the ExbB-ExbD complex from S. marcescens. ExbB alone is a stable pentamer, and its complex includes two ExbD monomers. We showed that ExbB extension interacts with HasB and is involved in heme acquisition and we identified key residues in the membrane domain of ExbB and ExbB, essential for function and likely involved in the interaction with TonB/HasB. Our results shed light on the class of inner membrane energy machinery formed by ExbB, ExbD and HasB.
Topics: Escherichia coli; Escherichia coli Proteins; Heme; Protein Binding; Serratia marcescens
PubMed: 35418619
DOI: 10.1038/s42003-022-03306-y -
The Journal of Biological Chemistry Sep 2023Serratia marcescens is an opportunistic human pathogen involved in antibiotic-resistant hospital acquired infections. Upon contact with the host epithelial cell and...
Serratia marcescens is an opportunistic human pathogen involved in antibiotic-resistant hospital acquired infections. Upon contact with the host epithelial cell and prior to internalization, Serratia induces an early autophagic response that is entirely dependent on the ShlA toxin. Once Serratia invades the eukaryotic cell and multiples inside an intracellular vacuole, ShlA expression also promotes an exocytic event that allows bacterial egress from the host cell without compromising its integrity. Several toxins, including ShlA, were shown to induce ATP efflux from eukaryotic cells. Here, we demonstrate that ShlA triggered a nonlytic release of ATP from Chinese hamster ovary (CHO) cells. Enzymatic removal of accumulated extracellular ATP (eATP) or pharmacological blockage of the eATP-P2Y2 purinergic receptor inhibited the ShlA-promoted autophagic response in CHO cells. Despite the intrinsic ecto-ATPase activity of CHO cells, the effective concentration and kinetic profile of eATP was consistent with the established affinity of the P2Y2 receptor and the known kinetics of autophagy induction. Moreover, eATP removal or P2Y2 receptor inhibition also suppressed the ShlA-induced exocytic expulsion of the bacteria from the host cell. Blocking α5β1 integrin highly inhibited ShlA-dependent autophagy, a result consistent with α5β1 transactivation by the P2Y2 receptor. In sum, eATP operates as the key signaling molecule that allows the eukaryotic cell to detect the challenge imposed by the contact with the ShlA toxin. Stimulation of P2Y2-dependent pathways evokes the activation of a defensive response to counteract cell damage and promotes the nonlytic clearance of the pathogen from the infected cell.
Topics: Animals; Cricetinae; Adenosine Triphosphate; Autophagy; CHO Cells; Cricetulus; Exocytosis; Host-Pathogen Interactions; Integrin alpha5beta1; Receptors, Purinergic P2Y2; Serratia; Toxins, Biological; Humans
PubMed: 37527778
DOI: 10.1016/j.jbc.2023.105119 -
Microbiology Spectrum Oct 2021The grass grub endemic to New Zealand, Costelytra giveni (Coleoptera: Scarabaeidae), and the manuka beetle, Pyronota festiva and P. setosa (Coleoptera: Scarabaeidae),...
Identification of Diverse Toxin Complex Clusters and an eCIS Variant in Serratia proteamaculans Pathovars of the New Zealand Grass Grub () and Manuka Beetle ( Spp.) Larvae.
The grass grub endemic to New Zealand, Costelytra giveni (Coleoptera: Scarabaeidae), and the manuka beetle, Pyronota festiva and P. setosa (Coleoptera: Scarabaeidae), are prevalent pest species. Through assessment of bacterial strains isolated from diseased cadavers of these insect species, 19 insect-active Serratia proteamaculans variants and a single Serratia entomophila strain were isolated. When independently bioassayed, these isolates differed in host range, the rate of disease progression, and 12-day mortality rates, which ranged from 60 to 100% of the challenged larvae. A spp.-derived S. proteamaculans isolate caused a transient disease phenotype in challenged C. giveni larvae, whereby larvae appeared diseased before recovering to a healthy state. Genome sequence analysis revealed that all but two of the sequenced isolates contained a variant of the S. entomophila amber-disease-associated plasmid, pADAP. Each isolate also encoded one of seven distinct members of the toxin complex (Tc) family of insect-active toxins, five of which are newly described, or a member of the extracellular contractile injection (eCIS) machine family, with a new AfpX variant designated SpF. Targeted mutagenesis of each of the predicted Tc- or eCIS-encoding regions abolished or attenuated pathogenicity. Host-range testing showed that several of the S. proteamaculans Tc-encoding isolates affected both and species, with other isolates specific for either spp. or The isolation of several distinct host-specific pathotypes of spp. may reflect pathogen-host speciation. New pathotypes of the insect pathogen , each with differing virulence attributes and host specificity toward larvae of the New Zealand manuka beetle and grass grub, have been identified. All of the Serratia proteamaculans isolates contained one of seven different insect-active toxin clusters or one of three eCIS variants. The diversity of these -encoded virulence clusters, resulting in differences in larval disease progression and host specificity in endemic scarab larvae, suggests speciation of these pathogens with their insect hosts. The differing virulence properties of these species may affect their potential infectivity and distribution among the insect populations. Based on their differing geographic isolation and pathotypes, several of these isolates, including the manuka beetle-active isolates, are likely to be more effective biopesticides in specific environments or could be used in combination for greater effect.
Topics: Animals; Bacterial Toxins; Biological Control Agents; Coleoptera; Genome, Bacterial; Host Specificity; Larva; New Zealand; Serratia; Virulence; Virulence Factors; Whole Genome Sequencing
PubMed: 34668742
DOI: 10.1128/Spectrum.01123-21 -
International Journal of Molecular... Sep 2020Bacteria of the genus inhabit a variety of ecological niches like water, soil, and the bodies of animals, and have a wide range of lifestyles. Currently, the complete...
Bacteria of the genus inhabit a variety of ecological niches like water, soil, and the bodies of animals, and have a wide range of lifestyles. Currently, the complete genome sequences of 25 phages are available in the NCBI database. All of them were isolated from nutrient-rich environments like sewage, with the use of clinical strains as hosts. In this study, we identified a novel myovirus named vB_SspM_BZS1. Both the phage and its host sp. OS31 were isolated from the same oligotrophic environment, namely, an abandoned gold mine (Zloty Stok, Poland). The BZS1 phage was thoroughly characterized here in terms of its genomics, morphology, and infection kinetics. We also demonstrated that sp. OS31 was lysogenized by mitomycin-inducible siphovirus vB_SspS_OS31. Comparative analyses revealed that vB_SspM_BZS1 and vB_SspS_OS31 were remote from the known phages. Moreover, vB_SspM_BZS1 was only distantly related to other viruses. However, we discovered similar prophage sequences in genomes of various bacteria here. Additionally, a protein-based similarity network showed a high diversity of phages in general, as they were scattered across nineteen different clusters. In summary, this work broadened our knowledge on the diverse relationships of phages.
Topics: Bacteriophages; DNA, Viral; Genome, Viral; Genomics; Gold; Phylogeny; Poland; Prophages; Serratia
PubMed: 32933193
DOI: 10.3390/ijms21186709