Leukotoxin Confers Beta-Hemolytic Activity to
            <i>Actinobacillus actinomycetemcomitans</i>

Balashova, Nataliya V.; Crosby, Juan A.; Ghofaily, Lourdes Al; Kachlany, Scott C.

doi:10.1128/iai.74.4.2015-2021.2006

Cited by 84 publications

(101 citation statements)

References 45 publications

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“…Interestingly, the ability of A. actinomycetemcomitans colonies to appear beta-hemolytic is dependent on the type of medium used (Fig. 3) and may explain why hemolysis was previously not observed (Balashova et al, 2006a). In contrast to cytolysis of WBCs, hemolysis appears to be non-specific, since human, sheep, and horse RBCs underwent lysis by LtxA, and hemolysis requires a higher dose of LtxA than the killing of WBCs.…”

Section: Ironmentioning

confidence: 89%

Aggregatibacter actinomycetemcomitansLeukotoxin

2010

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Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium that colonizes the human oral cavity and is the causative agent for localized aggressive periodontitis (LAP), an aggressive form of periodontal disease that occurs in adolescents. A. actinomycetemcomitans secretes a protein toxin, leukotoxin (LtxA), which helps the bacterium evade the host immune response during infection. LtxA is a membrane-active toxin that specifically targets white blood cells (WBCs). In this review, we discuss recent developments in this field, including the identification and characterization of genes and proteins involved in secretion, regulation of LtxA, biosynthesis, newly described activities of LtxA, and how LtxA may be used as a therapy for the treatment of diseases.

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Section: Ironmentioning

confidence: 89%

Aggregatibacter actinomycetemcomitansLeukotoxin

2010

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“…The remaining 2 genes, however, encoded less well recognized biofilm determinants-leukotoxin (ltxB [19]) and the DNA uptake transcriptional regulator TfoX (71). Leukotoxin is widely regarded as the primary virulence factor of A. actinomycetemcomitans, as it lyses both white and red blood cells (20), but recently it was also shown to control adherence. Specifically, disrupting ltxA diminishes tadA and pgaC expression and, as a result, binding to hydroxyapatite (calcium-based tooth mineral) (72).…”

Section: Discussionmentioning

confidence: 99%

Defining Genetic Fitness Determinants and Creating Genomic Resources for an Oral Pathogen

Narayanan

Ramsey

Stacy

et al. 2017

Appl Environ Microbiol

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Periodontitis is a microbial infection that destroys the structures that support the teeth. Although it is typically a chronic condition, rapidly progressing, aggressive forms are associated with the oral pathogen Aggregatibacter actinomycetemcomitans. One of this bacterium's key virulence traits is its ability to attach to surfaces and form robust biofilms that resist killing by the host and antibiotics. Though much has been learned about A. actinomycetemcomitans since its initial discovery, we lack insight into a fundamental aspect of its basic biology, as we do not know the full set of genes that it requires for viability (the essential genome). Furthermore, research on A. actinomycetemcomitans is hampered by the field's lack of a mutant collection. To address these gaps, we used rapid transposon mutant sequencing (Tn-seq) to define the essential genomes of two strains of A. actinomycetemcomitans, revealing a core set of 319 genes. We then generated an arrayed mutant library comprising Ͼ1,500 unique insertions and used a sequencing-based approach to define each mutant's position (well and plate) in the library. To demonstrate its utility, we screened the library for mutants with weakened resistance to subinhibitory erythromycin, revealing the multidrug efflux pump AcrAB as a critical resistance factor. During the screen, we discovered that erythromycin induces A. actinomycetemcomitans to form biofilms. We therefore devised a novel Tnseq-based screen to identify specific factors that mediate this phenotype and in follow-up experiments confirmed 4 mutants. Together, these studies present new insights and resources for investigating the basic biology and disease mechanisms of a human pathogen. IMPORTANCE Millions suffer from gum disease, which often is caused by Aggregatibacter actinomycetemcomitans, a bacterium that forms antibiotic-resistant biofilms. To fully understand any organism, we should be able to answer: what genes does it require for life? Here, we address this question for A. actinomycetemcomitans by determining the genes in its genome that cannot be mutated. As for the genes that can be mutated, we archived these mutants into a library, which we used to find genes that contribute to antibiotic resistance, leading us to discover that antibiotics cause A. actinomycetemcomitans to form biofilms. We then devised an approach to find genes that mediate this process and confirmed 4 genes. These results illuminate new fundamental traits of a human pathogen.KEYWORDS Aggregatibacter, Tn-seq, antibiotics, biofilms, essential genome O ne of the longest-studied human microbiomes is the "animalcules" (bacteria), first observed by van Leeuwenhoek (1), that inhabit the oral cavity. Oral bacteria readily attach to tooth surfaces and develop into spatially organized, multispecies biofilms (2). These communities also persist beneath the gum line in the subgingival pocket, where they are kept in check by host immune cells (3). Though normally benign, subgingival communities can accumulate opportunistic oral p...

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“…To determine if iron plays a role in LtxA regulation, we assayed betahemolysis under excess-iron and iron-limiting conditions on Columbia agar with 5% sheep blood (3). We found that, compared to results obtained with media with no added iron, betahemolysis was suppressed when A. actinomycetemcomitans was grown on Columbia agar containing 300 M FeCl 3 (Fig.…”

mentioning

confidence: 97%

Regulation of Aggregatibacter ( Actinobacillus ) actinomycetemcomitans Leukotoxin Secretion by Iron

et al. 2006

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The gram-negative oral and systemic pathogen Aggregatibacter (Actinobacillus) actinomycetemcomitans produces a leukotoxin (LtxA) that is a member of the RTX (repeats in toxin) family of secreted bacterial toxins. We have recently shown that LtxA has the ability to lyse erythrocytes, which results in a beta-hemolytic phenotype on Columbia blood agar. To determine if LtxA is regulated by iron, we examined beta-hemolysis under iron-rich and iron-limiting conditions. Beta-hemolysis was suppressed in the presence of FeCl 3 . In contrast, strong beta-hemolysis occurred in the presence of the iron chelator deferoxamine. We found that secretion of LtxA was completely inhibited by free iron, but expression of ltxA was not regulated by iron. Free chromium, cobalt, and magnesium did not affect LtxA secretion. Other LtxA-associated genes were not regulated by iron. Thus, iron appears to play an important role in the regulation of LtxA secretion in A. actinomycetemcomitans in a manner independent of gene regulation.

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Leukotoxin Confers Beta-Hemolytic Activity to Actinobacillus actinomycetemcomitans

Cited by 84 publications

References 45 publications

Aggregatibacter actinomycetemcomitansLeukotoxin

Aggregatibacter actinomycetemcomitansLeukotoxin

Defining Genetic Fitness Determinants and Creating Genomic Resources for an Oral Pathogen

Regulation of Aggregatibacter ( Actinobacillus ) actinomycetemcomitans Leukotoxin Secretion by Iron

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