Leiv Sigve Håvarstein's research while affiliated with Norwegian University of Life Sciences (NMBU) and other places
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Publications (104)
Infections caused by antibiotic-resistant Streptococcus pneumoniae are of growing concern for healthcare systems, which need new treatment options. Screening microorganisms in terrestrial environments has proved successful for discovering antibiotics, while production of antimicrobials by marine microorganisms remains underexplored. Here we have sc...
Competence development in the human pathogen Streptococcus pneumoniae controls several features such as genetic transformation, biofilm formation, and virulence. Competent bacteria produce so-called "fratricins" such as CbpD that kill noncompetent siblings by cleaving peptidoglycan (PGN). CbpD is a choline-binding protein (CBP) that binds to phosph...
Competence development in the human pathogen Streptococcus pneumoniae controls several features such as genetic transformation, biofilm formation and virulence. Competent bacteria produce so called fratricins such as CbpD, that kill non-competent siblings by cleaving peptidoglycan (PGN). CbpD is a choline-binding protein (CBP) that binds to phospho...
The ellipsoid shape of Streptococcus pneumoniae is determined by the synchronized actions of the elongasome and the divisome, which have the task of creating a protective layer of peptidoglycan (PG) enveloping the cell membrane. The elongasome is necessary for expanding PG in the longitudinal direction, whereas the divisome synthesizes the PG that...
Until recently class A penicillin‐binding proteins (aPBPs) were the only enzymes known to catalyze glycan chain polymerization from lipid II in bacteria. Hence, the discovery of two novel lipid II polymerases, FtsW and RodA, raises new questions and has consequently received a lot of attention from the research community. FtsW and RodA are essentia...
The ellipsoid shape of Streptococcus pneumoniae is determined by the synchronized actions of the elongasome and the divisome, which have the task of creating a protective layer of peptidoglycan (PG) enveloping the cell membrane. The elongasome is necessary for expanding PG in the longitudinal direction whereas the divisome synthesizes the PG that d...
Penicillin-binding proteins (PBPs), the proteins catalyzing the last steps of peptidoglycan assembly, are critical for bacteria to maintain cell size, shape, and integrity. PBPs are consequently attractive targets for antibiotics. Resistance to antibiotics in Streptococcus pneumoniae (the pneumococcus) are often associated with mutations in the PBP...
Bacterial cell division is a central process that requires exquisite orchestration of both the cell wall biosynthetic and lytic machineries. The essential membrane complex FtsEX, widely conserved across bacteria, plays a central role by recruiting proteins to the divisome apparatus and by regulating periplasmic muralytic activity from the cytosol....
FtsEX is a membrane complex widely conserved across diverse bacterial genera and involved in critical processes such as recruitment of division proteins and in spatial and temporal regulation of muralytic activity during cell division or sporulation. FtsEX is a member of the ABC transporter superfamily, where FtsX is an integral membrane protein an...
Significance
Peptidoglycan, the main structural component of the bacterial cell wall, is made of glycan strands cross-linked by short peptides. It has long been assumed that class A penicillin-binding proteins (PBPs) are the only enzymes capable of synthesizing glycan strands from lipid II. Recently, however, it was discovered that two non-PBP prot...
Streptococcus pneumoniae (pneumococci) is a leading cause of severe bacterial meningitis in many countries worldwide. To characterize the repertoire of fitness and virulence factors predominantly expressed during meningitis we performed niche-specific analysis of the in vivo proteome in a mouse meningitis model, in which bacteria are directly inocu...
In oval shaped Streptococcus pneumoniae , septal and longitudinal peptidoglycan synthesis is performed by independent functional complexes; the divisome and the elongasome. Penicillin binding proteins (PBPs) were long considered as the key peptidoglycan synthesizing enzymes in these complexes. Among these were the bifunctional class A PBPs, which a...
Studies of essential genes in bacteria are often hampered by the lack of accessible genetic tools. This is also the case for Lactobacillus plantarum , a key species in food and health applications. Here, we develop a clustered regularly interspaced short palindromic repeat interference (CRISPRi) system for knockdown of gene expression in L. plantar...
The RNA binding proteins EloR and KhpA are important components of the regulatory network that controls and coordinates cell elongation and division in S. pneumoniae. Loss of either protein reduces cell length, and makes the essential elongasome proteins PBP2b and RodA dispensable. It has been shown previously in formaldehyde crosslinking experimen...
FtsX is a ubiquitous bacterial integral membrane protein involved in cell division that regulates the activity of peptidoglycan (PG) hydrolases. FtsX is representative of a large group of ABC3 superfamily proteins that function as “mechanotransmitters,” proteins that relay signals from the inside to the outside of the cell. Here, we present a struc...
The RNA binding proteins EloR and KhpA are important components of the regulatory network that controls and coordinates cell elongation and division in S. pneumoniae . Loss of either protein reduce cell length, and makes the essential elongasome proteins PBP2b and RodA dispensable. It has been shown previously in formaldehyde crosslinking experimen...
Streptococcus pneumoniae is a leading killer of infants and immunocompromised adults and has become increasingly resistant to major antibiotics. Therefore, the development of new antibiotic strategies is desperately needed. Targeting bacterial cell division is one such strategy, specifically targeting essential proteins for the synthesis and breakd...
The universality of peptidoglycan in bacteria underlies the broad spectrum of many successful antibiotics. However, in our times of widespread resistance, the diversity of peptidoglycan modifications offers a variety of new antibacterials targets. In some Gram-positive species such as Streptococcus pneumoniae, Staphylococcus aureus, or Mycobacteriu...
The bacterial cell wall is in part composed of the peptidoglycan (PG) layer that maintains the cell shape and sustains the basic cellular processes of growth and division. The cell wall of Gram-positive bacteria also carries teichoic acids (TAs). In this work, we investigated how TAs contribute to the structuration of the PG network through the mod...
Staphylococcus aureus needs to control the position and timing of cell division and cell wall synthesis to maintain its spherical shape. We identified two membrane proteins, named CozEa and CozEb, which together are important for proper cell division in S. aureus. CozEa and CozEb are homologs of the cell elongation regulator CozESpn of Streptococcu...
Staphylococcus aureus needs to control the position and timing of cell division and cell wall synthesis to maintain its spherical shape. We identified two membrane proteins, named CozEa and CozEb, which together are important for proper cell division in S. aureus . CozEa and CozEb are homologs of the cell elongation regulator CozE Spn of Streptococ...
In a screen for mutations suppressing the lethal loss of PBP2b in Streptococcus pneumoniae we identified Spr1851 (named EloR), a cytoplasmic protein of unknown function whose inactivation removed the requirement for PBP2b as well as RodA. It follows from this that EloR and the two elongasome proteins must be part of the same functional network. Thi...
WalRK is the only two-component regulatory system essential for viability in Streptococcus pneumoniae. Despite its importance, the biological role of this system is not well understood. However, previous studies have shown that it has a crucial role in controlling pneumococcal cell division. Considerable efforts have been made to understand how the...
The important human pathogen Streptococcus pneumoniae is a naturally transformable species. When developing the competent state, it expresses proteins involved in DNA-uptake, DNA-processing and homologous recombination. In addition to the proteins required for the transformation process, competent pneumococci express proteins involved in a predator...
The oval shape of pneumococci results from a combination of septal and lateral peptidoglycan synthesis. The septal cross-wall is synthesized by the divisome, while the elongasome drives cell elongation by inserting new peptidoglycan into the lateral cell wall. Each of these molecular machines contains penicillin-binding proteins (PBPs), which catal...
Streptococcus pneumoniae is a frequent colonizer of the human nasopharynx that has the potential to cause severe infections such as pneumonia, bacteremia and meningitis. Despite considerable efforts to reduce the burden of pneumococcal disease, it continues to be a major public health problem. After the Second World War, antimicrobial therapy was i...
Staphylococcus aureus is a major human pathogen. Hospital infections caused by methicillin-resistant strains (MRSA), which have acquired resistance to a broad spectrum of antibiotics through horizontal gene transfer (HGT), are of particular concern. In S. aureus, virulence and antibiotic resistance genes are often encoded on mobile genetic elements...
Separation of daughter cells during bacterial cell division requires splitting of the septal cross wall by peptidoglycan hydrolases. In Streptococcus pneumoniae, PcsB is predicted to perform this operation. Recent evidence shows that PcsB is recruited to the septum by the transmembrane FtsEX complex, and that this complex is required for cell divis...
The biosynthesis of cell wall peptidoglycan is a complex process that involves six different penicillin-binding proteins (PBPs) in Streptococcus pneumoniae. Two of these, PBP2x and PBP2b, are monofunctional transpeptidases that catalyze the formation of peptide cross-links between adjacent glycan strands. Both of them are bitopic membrane proteins...
Streptococcus pneumoniae produces two class B penicillin-binding proteins, Pbp2x and Pbp2b, both of which are essential. It is generally assumed that Pbp2x is specifically involved in septum formation, while Pbp2b is dedicated to peripheral cell wall synthesis. However, little experimental evidence exists to substantiate this belief. In the present...
In the present work we have constructed a new tandem affinity purification tag and used it to purify two different polypeptides, PcsB and ECL1 from Streptococcus pneumoniae. PcsB probably functions as a peptidoglycan hydrolase and is believed to be involved in splitting of the septum during cell division. ECL1 is the extracellular domain of the mem...
Streptococcus pneumoniae and a number of commensal streptococcal species are competent for natural genetic transformation. The natural habitat of these bacteria is multispecies biofilms in the human oral cavity and nasopharynx. Studies investigating lateral transfer of virulence and antibiotic resistance determinants among streptococci have shown t...
Streptococcus pneumoniae protects itself from components of the human immune defense system by a thick polysaccharide capsule, which in most serotypes is covalently attached to the cell wall peptidoglycan. Members of the LytR-Cps2A-Psr (LCP) protein family have recently been implicated in the attachment of anionic polymers to peptidoglycan in Gram-...
Competence for natural genetic transformation is widespread in the genus Streptococcus. The current view is that all streptococcal species possess this property. In addition to the proteins required for DNA uptake
and recombination, competent streptococci secrete muralytic enzymes termed fratricins. Since the synthesis and secretion of
these cell w...
Recently it has been shown that Streptococcus thermophilus is competent for natural genetic transformation. This property is widespread among streptococci and may include all members of the genus. Upon entering the competent state, streptococci start transcribing a number of competence-specific genes whose products are required for binding, uptake...
Streptococcus pneumoniae and probably most other members of the genus Streptococcus are competent for natural genetic transformation. During the competent state, S. pneumoniae produces a murein hydrolase, CbpD, that kills and lyses noncompetent pneumococci and closely related species. Previous studies
have shown that CbpD is essential for efficient...
To facilitate the study of pneumococcal genes that are essential for viability or normal cell growth, we sought to develop
a tightly regulated, titratable gene depletion system that interferes minimally with normal cellular functions. A possible
candidate for such a system is the recently discovered signal transduction pathway regulating competence...
The alternative sigma factor ComX is a key regulator of natural transformation in members of the genus Streptococcus. ComX controls expression of the late competence genes, which are essential for DNA binding, uptake and recombination. In Streptococcus pneumoniae, it has been demonstrated that ComX is degraded by ClpEP at the end of the competence...
Streptococcus pneumoniae is one of the most important model organisms for studies on natural genetic transformation in bacteria. The prevalence of this gene exchange mechanism in the genus Streptococcus has not been subjected to systematic investigations, but it has been known for decades that only a few streptococcal species develop the competent...
In the Firmicutes, two-component regulatory systems of the LiaSR type sense and orchestrate the response to various agents that perturb cell
envelope functions, in particular lipid II cycle inhibitors. In the current study, we found that the corresponding system
in Streptococcus pneumoniae displays similar properties but, in addition, responds to c...
To develop a general method for site-directed mutagenesis in the dairy starter strain Streptococcus thermophilus LMG 18311 which does not depend on antibiotic-resistance genes or other selection markers for the identification of transformants.
In a previous study, we demonstrated that Strep. thermophilus LMG 18311 can be made competent for natural...
Pneumococci that are competent for natural genetic transformation express a number of proteins involved in binding, uptake, translocation and recombination of DNA. In addition, they attack and lyse non-competent sister cells present in the same environment. This phenomenon has been termed fratricide. The key effector of pneumococcal fratricide is C...
[This corrects the article on p. e2683 in vol. 3.].
The ability of pneumococci to take up naked DNA from the environment and permanently incorporate the DNA into their genome by recombination has been exploited as a valuable research tool for 80 years. From being viewed as a marginal phenomenon, it has become increasingly clear that horizontal gene transfer by natural transformation is a powerful me...
Pneumococci that have developed the competent state kill and lyse non-competent sister cells and members of closely related species during co-cultivation in vitro. The key component in this process, called fratricide, is the product of the late competence gene cbpD. In addition, the peptidoglycan hydrolases LytA and LytC are required for efficient...
Proliferation of the human-pathogenic bacterium Streptococcus pneumoniae is fundamentally linked to the bacterial proteins that function in cell division. Here, we show that LytR, a pneumococcal
protein from the LytR-CpsA-Psr family, is essential to this process.
Bacteria that are competent for natural genetic transformation, such as pneumococci and their commensal relatives Streptococcus mitis and Streptococcus oralis, take up exogenous DNA and incorporate it into their genomes by homologous recombination. Traditionally, it has been assumed that genetic material leaking from dead bacteria constitutes the s...
![Figure 3. Map of S. pneumoniae genomes [8–44,45] and the unfinished S....](profile/Mogens-Kilian-2/publication/51403824/figure/fig1/AS:394110121857024@1470974583166/Map-of-S-pneumoniae-genomes-8-44-45-and-the-unfinished-S-mitis-genome-JCVI-CMR-in_Q320.jpg)
Streptococcus pneumoniae is a member of the Mitis group of streptococci which, according to 16S rRNA-sequence based phylogenetic reconstruction, includes 12 species. While other species of this group are considered prototypes of commensal bacteria, S. pneumoniae is among the most frequent microbial killers worldwide. Population genetic analysis of...
Primers used for PCR amplification and sequencing of genes.
(0.03 MB DOC)
Phylogenetic tree constructed with the minimum evolution algorithm and based on partial sequences of individual 16S rRNA genes (439 to 449 nucleotides corresponding to positions 51 to 493 in the Escherichia coli 16S rRNA gene in 4 strains showing sequence polymorphism among the four individual rRNA operons labeled A through D. Sequences obtained fo...
Phylogenetic tree constructed with the minimal evolution algorithm and based on partial 16S rRNA gene sequences of 80 strains of mitis group streptococci. Type strains are shown with species designation. The settings in the program MEGA 3.1 were as follows: Gaps/missing: pairwise deletions; Distance method: Nucleotide: Tamura and Nei (Gamma = 1). B...
Strains analyzed in the study with site of isolation, origin, and previous designation.
(0.29 MB DOC)
Gene organization of the cap locus between dexB and aliA and flanking regions in S. mitis NCTC12261 compared with S. pneumoniae strains D39, G54, and TIGR4.
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Amino acid sequence of competence stimulating peptides (CSPs) from strains of streptococci assigned to species according to the cluster analysis in Fig. 1 (SK strains) or as indicated in previously publications. Cluster-specific amino acid signatures within the leader sequence are summarized in Table 1.
(0.11 MB DOC)
Phenotypic properties and BoxB and insertion sequence elements among S. pneumoniae, S. pseudopneumoniae, and S. mitis strains illustrating genome reduction in S. mitis
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Studies show that gene acquisition through natural transformation has contributed significantly to the adaptation and ecological diversification of several bacterial species. Relatively little is still known, however, about the prevalence and phylogenetic distribution of organisms possessing this property. Thus, whether natural transformation only...
Competence for natural genetic transformation in Streptococcus pneumoniae is controlled by the extracellular concentration of the competence-stimulating peptide (CSP), an exported peptide pheromone. Upon entering the competent state, pneumococci start transcribing a number of CSP-responsive genes, termed the early and late competence (com) genes. S...
Cannibalism and fratricide refer to the killing of genetically identical cells (siblings) that was recently documented in two Gram-positive species, Bacillus subtilis and Streptococcus pneumoniae, respectively. Cannibalism occurs during the early stages of sporulation in B. subtilis, whereas fratricide occurs in S. pneumoniae during natural genetic...
A locus encoding proteins with high homology to the pneumococcal BlpABCHR quorum-sensing system was identified in Streptococcus thermophilus LMG 18311. The BlpABCHR system regulates bacteriocin production in Streptococcus pneumoniae by monitoring the extracellular concentration of a peptide-pheromone encoded by blpC. The homologous system in S. the...
More than 100 BOX elements are randomly distributed in intergenic regions of the pneumococcal genome. Here we demonstrate
that these elements can affect expression of neighboring genes and present evidence that they are mobile. Together, our findings
show that BOX elements enhance genetic diversity and genomic plasticity in Streptococcus pneumoniae...
Streptococcus thermophilus is widely used for the manufacture of yoghurt and Swiss or Italian-type cheeses. These products have a market value of approximately
$40 billion per year, making S. thermophilus a species that has major economic importance. Even though the fermentation properties of this bacterium have been gradually
improved by classical...
In 1971, Tomasz and Zanati discovered that competent pneumococci have a tendency to form aggregates when pelleted by centrifugation and resuspended in 0.01 N HCl by brief vortexing. Interestingly, no clumping was observed with parallel cultures of non-competent cells treated in the same way. We set out to elucidate the mechanism behind this strikin...
Induction of competence for natural genetic transformation in Streptococcus pneumoniae depends on pheromone-mediated cell-cell communication and a signaling pathway consisting of the competence-stimulating peptide (CSP), its membrane-embedded histidine kinase receptor ComD, and the cognate response regulator ComE. Extensive screening of pneumococca...
Streptococcus pneumoniae is an important human pathogen that is able to take up naked DNA from the environment by a quorum-sensing-regulated process
called natural genetic transformation. This property enables members of this bacterial species to efficiently acquire new
properties that may increase their ability to survive and multiply in the human...
Streptococcus pneumoniae secretes two different peptide pheromones used for intercellular communication. These peptides, which have completely unrelated
primary structures, activate two separate signal transduction pathways, ComABCDE and BlpABCSRH, which regulate natural genetic
transformation and bacteriocin production, respectively. Each signal t...
The stability of microbial genomes is constantly challenged by horizontal gene transfer, recombination and DNA damage. Mechanisms for rapid genome variation, adaptation and maintenance are a necessity to ensure microbial fitness and survival in changing environments. Indeed, genome sequences reveal that most, if not all, bacterial species have nume...
Several streptococcal species are able to take up naked DNA from the environment and integrate it into their genomes by homologous recombination. This process is called natural transformation. In Streptococcus pneumoniae and related streptococcal species, competence for natural transformation is induced by a peptide pheromone through a quorum-sensi...
Intercellular communication mediated by peptide pheromones controls several different biological processes in gram-positive bacteria, such as virulence and horizontal gene transfer. Pheromone binding results in autophosphorylation of the histidine kinase receptor, followed by transfer of the phosphoryl group to the cognate cytoplasmic response regu...
Bacteria, which often are subjected to fluctuations in nutrients, temperature, radiation, pH, etc., adapt to the physico-chemical environment they live in by making the appropriate changes in their gene expression patterns. During the last decades it has become increasingly clear that bacteria, in addition, have a "social life", and that changes in...
Lactic acid bacteria (LAB) fight competing Gram-positive microorganisms by secreting anti-microbial peptides called bacteriocins. Peptide bacteriocins are usually divided into lantibiotics (class I) and non-lantibiotics (class II), the latter being the main topic of this review. During the past decade many of these bacteriocins have been isolated a...
Many streptococcal species belonging to the mitis and anginosus phylogenetic groups are known to be naturally competent for
genetic transformation. Induction of the competent state in these bacteria is regulated by a quorum-sensing mechanism consisting
of a secreted peptide pheromone encoded by comC and a two-component regulatory system encoded by...
Naturally competent bacteria have the ability to take up free DNA from the surrounding medium and incorporate this DNA into their genomes by homologous recombination. In naturally competent Streptococcus pneumoniae, and related streptococcal species from the mitis phylogenetic group, the competent state is not a constitutive property but is induced...
Enterococcus faecium L50 grown at 16 to 32 degrees C produces enterocin L50 (EntL50), consisting of EntL50A and EntL50B, two unmodified non-pediocin-like peptides synthesized without an N-terminal leader sequence or signal peptide. However, the bacteriocin activity found in the cell-free culture supernatants following growth at higher temperatures...
Natural competence in Streptococcus pneumoniae is regulated by a quorum-sensing mechanism consisting of a competence-stimulating peptide (CSP), its dedicated secretion apparatus (ComAB), its histidine kinase receptor (ComD) and a response regulator (ComE). In this report, we show that ComE is a DNA-binding protein that acts autocatalytically by bin...
In Lactobacillus plantarum C11, bacteriocin production has previously been shown to be an inducible process, in which a secreted peptide, produced by the host itself, is involved. The inducing factor, designated plantaricin A (PlnA), is a bacteriocin-like peptide encoded by a gene (plnA) located on the same operon as the genes for a two-component r...
Natural competence in the genus Streptococcus is not limited to S. pneumoniae. In general, all streptococci belonging to the mitis and anginosus groups, as well as some strains of Streptococcus mutans, possess this property[9xSee all References, 12xHavarstein, L.S., Hakenbeck, R., and Gaustad, P. J. Bacteriol. 1997; 179: 6589–6594PubMedSee all Refe...
Enterocin L50 (EntL50), initially referred to as pediocin L50 (L. M. Cintas, J. M. Rodríguez, M. F. Fernández, K. Sletten, I. F. Nes, P. E. Hernández, and H. Holo, Appl. Environ. Microbiol. 61:2643-2648, 1995), is a plasmid-encoded broad-spectrum bacteriocin produced by Enterococcus faecium L50. It has previously been purified from the culture supe...
Enterocin P is a new bacteriocin produced by Enterococcus faecium P13 isolated from a Spanish dry-fermented sausage. Enterocin P inhibited most of tested spoilage and food-borne gram-positive pathogenic bacteria, such as Listeria monocytogenes, Staphylococcus aureus, Clostridium perfringens, and Clostridium botulinum. Enterocin P is produced during...
To map the incidence of natural competence in the genus Streptococcus, we used PCR to screen a number of streptococcal strains for the presence of the recently identified competence regulation operon, containing the comC, -D, and -E genes. This approach established that the operon is present in strains belonging to the S. mitis and S. anginosus gro...
A large number of new bacteriocins in lactic acid bacteria (LAB) has been characterized in recent years. Most of the new bacteriocins belong to the class II bacteriocins which are small (30–100 amino acids) heat-stable and commonly not post-translationally modified. While most bacteriocin producers synthesize only one bacteriocin, it has been shown...
The nucleotide sequence of comC, the gene encoding the 17-residue competence-stimulating peptide (CSP) of Streptococcus pneumoniae (L. S. Havarstein, G. Coomaraswamy, and D. A. Morrison, Proc. Natl. Acad. Sci. USA 92:11140-11144, 1995) was determined with 42 encapsulated strains of different serotypes. A new allele, comC2, was found in 13 strains,...
Competence for genetic transformation in certain species of streptococci has been known for many years to be induced by a secreted protease-sensitive pheromone, referred to as the competence factor or activator, which acts as a quorum-sensing signal to co-ordinate expression of late competence genes. We recently reported identification of the phero...
The regulation of competence for genetic transformation in Streptococcus pneumoniae depends on a quorum-sensing system, but the only molecular elements of the system whose specific role have been identified are an extracellular peptide signal and an ABC-transporter required for its export. Here we show that transcription of comC, the gene encoding...
Lactobacillus plantarum C11 secretes a small cationic peptide, plantaricin A, that serves as induction signal for bacteriocin production as well as transcription of plnABCD. The plnABCD operon encodes the plantaricin A precursor (PlnA) itself and determinants (PlnBCD) for a signal transducing pathway. By Northern (RNA) and sequencing analyses, four...
A new bacteriocin has been isolated from an Enterococcus faecium strain. The bacteriocin, termed enterocin A, was purified to homogeneity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, N-terminal amino acid sequencing, and mass spectrometry analysis. By combining the data obtained from amino acid and DNA sequencing, the pri...
Competence for genetic transformation in Streptococcus pneumoniae has been known for three decades to arise in growing cultures at a critical cell density, in response to a secreted protease-sensitive signal. We show that strain CP1200 produces a 17-residue peptide that induces cells of the species to develop competence. The sequence of the peptide...
In this study, we show that bacteriocin production in Lactobacillus plantarum C11 is an inducible process triggered by a secreted protein factor produced by the bacteriocin producer itself. The induction factor was identified to be plantaricin A, a bacteriocin-like peptide whose gene (plnA) is located in the same operon as a two-component regulator...
Lantibiotic and non-lantibiotic bacteriocins are synthesized as precursor peptides containing N-terminal extensions (leader peptides) which are cleaved off during maturation. Most non-lantibiotics and also some lantibiotics have leader peptides of the so-called double-glycine type. These leader peptides share consensus sequences and also a common p...
Colicin V is a ribosomally synthesized antimicrobial peptide produced by Escherichia coli. Four recently characterized genes, arranged in two convergent operons on the plasmid pCoIV-K30, are required for colicin V synthesis, export and immunity. We report the purification and N-terminal amino acid sequencing of the colicin V protein. Our results de...
Purification and amino acid sequencing of plantaricin A, a bacteriocin from Lactobacillus plantarum C11, revealed that maximum bacteriocin activity is associated with the complementary action of two almost-identical peptides, alpha and beta (J. Nissen-Meyer, A. G. Larsen, K. Sletten, M. Daeschel, and I. F. Nes, J. Gen. Microbiol. 139:1973-1978, 199...
Citations
... V11A did not affect the growth of other bacterial colonizers of the nasopharynx tested: S. mitis, H. influenzae, S. aureus or K. pneumoniae. Another proteinaceous interspecies molecule from the genus Lysinibacillus was found previously, which depends on the Ami permease for growth inhibition of not only S. pneumoniae but also S. mitis 26 . V11A therefore appears to have a more species-specific effect. ...
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... Bacterial surface polysaccharides also influence transformation capacity (Weiser and Kapoor, 1999;Li et al., 2019;Minhas et al., 2023). For example, the pneumococcal cell envelope that is primarily composed of capsular polysaccharides (CPS) may impede DNA uptake and hence influence transformation (Weiser and Kapoor, 1999). ...
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... However, the emergence of penicillin-resistant bacterial species has led to the exploration of other antibiotics [4]. Te increase in N. gonorrhoeae strains exhibiting intermediate resistance to routinely prescribed antigonococcal medication poses their specifc structural and functional characteristics [3,9]. Comprehending the transpeptidase function of PBPs in classes A and B is essential for promoting the creation of peptide cross-links between adjacent peptidoglycan strands. ...
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... As shown in Table 2, a total of 41 proteins showed a significant difference in enrichment and were regarded as the potential proteins interacting with DivIVA. These proteins include MltG, a recently identified member of elongasome involved in cell extension, and its deletion makes cells shorter and suppresses the need for PBP2b protein (37). We next verified the DivIVA-MltG interaction, using a T18-T25-based bacterial two-hybrid (BTH) system. ...
... Later studies have also indicated functional interactions with additional morphogen esis factors, such as RodZ (24). A CozE paralog in S. pneumoniae, named CozEb, has also been found to be part of the same complex as CozE (24,25), and there seems to be a complex interplay between the two paralogs (24,25); individual deletions of cozE or cozEb in S. pneumoniae generated different phenotypes with regard to cell shape and growth inhibition, and while CozEb was not required for correct localization of PBP1a, overexpression of this protein could compensate for deletion of cozE, suppressing both growth and morphology defects. ...
... FtsE and FtsX are essential cell division proteins which interact with and control the www.nature.com/scientificreports/ peptidoglycan hydrolyse PcsB which separates daughter cells 26,27 . Their downregulation by the peptides might be a consequence of reduced growth which would require less expression of the daughter cell splitting machinery. ...
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... For practical applications in docking studies, certain microbial enzymes and proteins that are critical for pathogen survival and virulence can be targeted. Examples include DNA Gyrase (Bacterial Topoisomerase II), essential for bacterial DNA replication [63][64][65]; β-ketoacyl-ACP Synthase (FabB/FabF), involved in bacterial fatty acid synthesis [66][67][68]; Lanosterol 14αdemethylase (CYP51), crucial in fungal ergosterol biosynthesis [69,70]; and Penicillin-Binding Proteins (PBPs), key components in bacterial cell wall synthesis [71][72][73][74]. Targeting these proteins can potentially lead to the discovery of novel antimicrobial agents that are effective against resistant strains of bacteria and fungi. ...
... The Ami system has been proposed to play a significant role in environmental signaling, the initiation of competence [11], as well as contributing to the successful colonization of the nasopharynx [23]. AliB, but not AmiA or AliA, is associated with meningitis [24]; suggesting that AliB may possess a distinct oligopeptide substrate specificity that cannot be compensated by AmiA or AliA. Notably, in the absence of capsular polysaccharides and PspK, group II NESp strains harboring aliC and aliD within the deleted cps locus, are still capable of nasopharyngeal colonization [9,[25][26][27]. ...
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... Subsequent studies have confirmed this function in different species. In both S. pneumoniae and Lactobacillus plantarum , deletion or knockdown of khpA and khpB leads to decreased cell size (55)(56)(57). To examine if this function is conserved in F. nucleatum , we characterized cellular morphology of all deletion strains. ...
... Subsequent studies have confirmed this function in different species. In both S. pneumoniae and Lactobacillus plantarum , deletion or knockdown of khpA and khpB leads to decreased cell size (55)(56)(57). To examine if this function is conserved in F. nucleatum , we characterized cellular morphology of all deletion strains. ...
