Virulence factors of Aggregatibacter actinomycetemcomitans - A status update

Malik, Rajvir; Changela, Radha; Krishan, Prerna; Gugnani, Shalini; Bali, Deepika

doi:10.4103/2231-0754.164390

Cited by 11 publications

(13 citation statements)

References 3 publications

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“…Amongst all periodontal bacteria, A . actinomycetemcomitans was chosen for this study because of its virulence, difficulty of treatmeant [23] and ability to resist antibiotics [24, 25].…”

Section: Discussionmentioning

confidence: 99%

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Synergistic effects of LFchimera and antibiotic against planktonic and biofilm form of Aggregatibacter actinomycetemcomitans

et al. 2019

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Adjunctive use of antibiotics in periodontal treatment have limitations and disadvantages including bacterial resistance. Antimicrobial peptides (AMPs) are potential new agents that can combat bacterial infection. In this study, antimicrobial activity of different concentrations of conventional antibiotics minocycline (MH), doxycycline (DOX), and antimicrobial peptides LL-37, LL-31, Lactoferrin chimera (LFchimera) and Innate Defense Regulator Peptide 1018 (IDR-1018) against Aggregatibacter actinomycetemcomitans ATCC 43718 were determined using colony culturing assay. Subsequently, in vitro activity of the most effective drug and peptide combination was evaluated by checkerboard technique. Impact of the drug and peptide co-administration on biofilm at different stages, i.e., during adhesion and 1-day old biofilm was compared to each of the agents used alone. Results revealed that the killing effects of all AMPs range from 13–100%. In contrast, MH and DOX at 1 and 5 μM showed no killing activity and instead stimulated growth of bacteria. DOX has better killing activity than MH. LFchimera displayed the strongest killing amongst the peptides. Checkerboard technique revealed that combining DOX and LFchimera yielded synergism. Confocal laser scanning microscopy further showed that the combination of DOX and LFchimera caused significant reduction of bacterial adhesion and reduction of biomass, average biofilm thickness and substratum biofilm coverage of 1-day old biofilm compared to DOX and LFchimera alone. In conclusion, LFchimera alone and in combination with DOX exhibited strong antibacterial and anti-biofilm property against A . actinomycetemcomitans . The findings suggest that LFchimera should be considered for development as a new potential therapeutic agent that may be used as an adjunctive treatment for periodontitis.

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“…Amongst all periodontal bacteria, A . actinomycetemcomitans was chosen for this study because of its virulence, difficulty of treatmeant [23] and ability to resist antibiotics [24, 25].…”

Section: Discussionmentioning

confidence: 99%

“…A . actinomycetemcomitans have multiple adhesins including fimbriae, extracellular amorphous material and invasins present on its cell wall [25] that contributes to its virulence. One possible therapeutic approach preventing or treating disease is by interfering bacterial adhesion.…”

Section: Discussionmentioning

confidence: 99%

Synergistic effects of LFchimera and antibiotic against planktonic and biofilm form of Aggregatibacter actinomycetemcomitans

et al. 2019

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“…The original habitat of this bacterium is the oral cavity. Other bacteria that can cause periodontal disease are Porphyromonas gingivalis, Prevotela intermedia, and Fusobacterium nucleatum which are a Gram-negative bacteria [6,17,18]. However, the most dominant bacteria found in periodontitis is the bacterium Aa [19].…”

Section: Discussionmentioning

confidence: 99%

The Effectiveness of Soursop Leaf Extract Against Growth of Aggregatibacter Actinomycetemcomitans Atcc® 6514™ in Vitro

Primasari

Nasution

Arbi

et al. 2018

Asian J Pharm Clin Res

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Objective: The objective of this study was to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) antibacterial power of soursop leaf extract on Aggregatibacter actinomycetemcomitans (Aa) ATCC ® 6514™ growth. Methods:This study was experimental laboratory with post-test only control group design and consists of 8 treatment groups that were soursop leaf extract group with concentration 50%, 25%, 12.5%, 6.25%, 3.125%, and 1.5625% as well as negative control groups were brain heart infusion broth (BHIB) media and chlorhexidine as positive controls. Each treatment was done 3 repetitions. Testing the effectiveness of soursop leaf extract using dilution methods on BHIB and subculture media on Mueller Hinton Agar (MHA) media. The number of Aa ATCC ® 6514 ™ colonies was calculated manually using the total plate count method on the MHA media. Data were analyzed using Kruskal-Wallis test (p<0.05) followed by least significance different (LSD) test to see the significant mean difference between treatment groups.Results: Concentration of MIC from soursop leaf extract on Aa ATCC ® 6514™ growth was 1.5625% and MBC was 6.25%. LSD assay results showed significant difference effect (p<0.05) Aa ATCC ® 6514™ from each treatment group. Conclusion:Soursop leaf extract has antibacterial effectivity against Aa ATCC ® 6514 ™.

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“…Like other Gram‐negative bacteria, A. actinomycetemcomitans is known to secrete a protein toxin, leukotoxin (LtxA) which allows its ability to evade the immune response of host during infection; hence, it has been recognized as a major virulence factor . This, in addition to other factors, basically enhances its oral‐cavity survival, enabling it to circumvent the protective strategies of the host . Its mechanism of production and secretion has been previously described in detail .…”

Section: Introductionmentioning

confidence: 99%

“…9,10 This, in addition to other factors, basically enhances its oralcavity survival, enabling it to circumvent the protective strategies of the host. 11 Its mechanism of production and secretion has been previously described in detail. 2,12 LtxA is a 116-kDa protein and member of the RTX family of toxins and shares similar genome organization and structures with the RTX proteins secreted by other Gram-negative bacteria.…”

Section: Introductionmentioning

confidence: 99%

Solving the riddle: Unraveling the mechanisms of blocking the binding of leukotoxin by therapeutic antagonists in periodontal diseases

Abdullahi

Olotu

Soliman

2018

J of Cellular Biochemistry

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Aggregatibacter actinomycetemcomitans is a Gram-negative bacteria that has gained wide recognition for its causative role in the development of various immune diseases, which includes localized aggressive periodontitis. Its ability to evade host defense mechanisms is mediated by the secretion of leukotoxin (LtxA), which induces death of white blood cells (leukocytes) by specific binding to their surface-expressed leukocyte function-associated receptor (LFA-1) in its active state. Therapeutic compounds that interfere with this pathogenic process and abrogate A. actinomycetemcomitans virulence have been reported in literature. These include doxycycline, and more recently phytochemical compounds such as hamamelitanin, resveratrol, naringin, and quercetin. However, the question remains how do they work? Therefore, with the aid of computational tools, we explore the molecular mechanisms by which they possibly elicit their therapeutic functions. Molecular mechanics Poisson/Boltzmann surface area analyses revealed that these compounds bind favorably to active LFA-1 with high affinity and considerable stability, indicative of their ability to occupy the LtxA binding site (LBS) and prevent LtxA binding. The conformational transition of open LFA-1 to its closed state further describe the mechanistic activity of these compounds. In addition to notable reductions in structural mobility and flexibility, the burial of surface-exposed interactive side chains at the LBS was observed, an occurrence that could alter the complementary binding of LtxA. It is also important to mention that these occurrences were induced more prominently by the phytochemicals. We believe that these findings will enhance the scope of drug design and discovery for potent LtxA antagonists with improved activities and therapeutic efficacies in the treatment of virulent A. actinomycetemcomitans diseases.

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Virulence factors of Aggregatibacter actinomycetemcomitans - A status update

Cited by 11 publications

References 3 publications

Synergistic effects of LFchimera and antibiotic against planktonic and biofilm form of Aggregatibacter actinomycetemcomitans

Synergistic effects of LFchimera and antibiotic against planktonic and biofilm form of Aggregatibacter actinomycetemcomitans

The Effectiveness of Soursop Leaf Extract Against Growth of Aggregatibacter Actinomycetemcomitans Atcc® 6514™ in Vitro

Solving the riddle: Unraveling the mechanisms of blocking the binding of leukotoxin by therapeutic antagonists in periodontal diseases

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