scholarly journals Mycobacterium abscessus Smooth and Rough Morphotypes Form Antimicrobial-Tolerant Biofilm Phenotypes but Are Killed by Acetic Acid

2018 ◽  
Vol 62 (3) ◽  
Author(s):  
Gillian Clary ◽  
Smitha J. Sasindran ◽  
Nathan Nesbitt ◽  
Laurel Mason ◽  
Sara Cole ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Intracellular Survival ◽  
Mycobacterium Abscessus ◽  
Human Macrophage ◽  
Content Type ◽  
Prevailing Paradigm ◽  
Chronic Pulmonary Diseases ◽  
The Face

ABSTRACT Mycobacterium abscessus has emerged as an important pathogen in people with chronic inflammatory lung diseases such as cystic fibrosis, and recent reports suggest that it may be transmissible by fomites. M. abscessus exhibits two major colony morphology variants: a smooth morphotype ( Ma Sm ) and a rough morphotype ( Ma Rg ). Biofilm formation, prolonged intracellular survival, and colony variant diversity can each contribute to the persistence of M. abscessus and other bacterial pathogens in chronic pulmonary diseases. A prevailing paradigm of chronic M. abscessus infection is that Ma Sm is a noninvasive, biofilm-forming, persistent phenotype and Ma Rg an invasive phenotype that is unable to form biofilms. We show that Ma Rg is hyperaggregative and forms biofilm-like aggregates, which, like Ma Sm biofilm aggregates, are significantly more tolerant than planktonic variants to acidic pHs, hydrogen peroxide (H 2 O 2 ), and treatment with amikacin or azithromycin. We further show that both variants are recalcitrant to antibiotic treatment inside human macrophage-like cells and that Ma Rg is more refractory than Ma Sm to azithromycin. Our results indicate that biofilm-like aggregation and protracted intracellular survival may each contribute to the persistence of this problematic pathogen in the face of antimicrobial agents regardless of morphotype. Biofilms of each M. abscessus variant are rapidly killed, however, by acetic acid, which may help to prevent local fomite transmission.

Environment in the lung of cystic fibrosis patients stimulates the expression of biofilm phenotype in Mycobacterium abscessus

2022 ◽  
Vol 71 (1) ◽  
Author(s):  
Bailey F. Keefe ◽  
Luiz E. Bermudez
Keyword(s):  
Cystic Fibrosis ◽  
Host Cell ◽  
Biofilm Formation ◽  
Type Species ◽  
Divalent Cations ◽  
Mycobacterium Abscessus ◽  
Content Type ◽  
Link Type ◽  
Populations At Risk

Introduction. Pulmonary infections caused by organisms of the Mycobacterium abscessus complex are increasingly prevalent in populations at risk, such as patients with cystic fibrosis, bronchiectasis and emphysema. Hypothesis. M. abscessus infection of the lung is not observed in immunocompetent individuals, which raises the possibility that the compromised lung environment is a suitable niche for the pathogen to thrive in due to the overproduction of mucus and high amounts of host cell lysis. Aim. Evaluate the ability of M. abscessus to form biofilm and grow utilizing in vitro conditions as seen in immunocompromised lungs of patients. Methodology. We compared biofilm formation and protein composition in the presence and absence of synthetic cystic fibrosis medium (SCFM) and evaluated the bacterial growth when exposed to human DNA. Results. M. abscessus is capable of forming biofilm in SCFM. By eliminating single components found in the medium, it became clear that magnesium works as a signal for the biofilm formation, and chelation of the divalent cations resulted in the suppression of biofilm formation. Investigation of the specific proteins expressed in the presence of SCFM and in the presence of SCFM lacking magnesium revealed many different proteins between the conditions. M. abscessus also exhibited growth in SCFM and in the presence of host cell DNA, although the mechanism of DNA utilization remains unclear. Conclusions. In vitro conditions mimicking the airways of patients with cystic fibrosis appear to facilitate M. abscessus establishment of infection, and elimination of magnesium from the environment may affect the ability of the pathogen to establish infection.

scholarly journals Apple Flavonoid Phloretin Inhibits Escherichia coli O157:H7 Biofilm Formation and Ameliorates Colon Inflammation in Rats

2011 ◽  
Vol 79 (12) ◽  
pp. 4819-4827 ◽  
Author(s):  
Jin-Hyung Lee ◽  
Sushil Chandra Regmi ◽  
Jung-Ae Kim ◽  
Moo Hwan Cho ◽  
Hyungdon Yun ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Trinitrobenzene Sulfonic Acid ◽  
Content Type ◽  
E Coli ◽  
Colon Inflammation ◽  
K 12

ABSTRACTPathogenic biofilms have been associated with persistent infections due to their high resistance to antimicrobial agents, while commensal biofilms often fortify the host's immune system. Hence, controlling biofilm formation of both pathogenic bacteria and commensal bacteria is important in bacterium-related diseases. We investigated the effect of plant flavonoids on biofilm formation of enterohemorrhagicEscherichia coliO157:H7. The antioxidant phloretin, which is abundant in apples, markedly reducedE. coliO157:H7 biofilm formation without affecting the growth of planktonic cells, while phloretin did not harm commensalE. coliK-12 biofilms. Also, phloretin reducedE. coliO157:H7 attachment to human colon epithelial cells. Global transcriptome analyses revealed that phloretin repressed toxin genes (hlyEandstx2), autoinducer-2 importer genes (lsrACDBF), curli genes (csgAandcsgB), and dozens of prophage genes inE. coliO157:H7 biofilm cells. Electron microscopy confirmed that phloretin reduced fimbria production inE. coliO157:H7. Also, phloretin suppressed the tumor necrosis factor alpha-induced inflammatory responsein vitrousing human colonic epithelial cells. Moreover, in the rat model of colitis induced by trinitrobenzene sulfonic acid (TNBS), phloretin significantly ameliorated colon inflammation and body weight loss. Taken together, our results suggest that the antioxidant phloretin also acts as an inhibitor ofE. coliO157:H7 biofilm formation as well as an anti-inflammatory agent in inflammatory bowel diseases without harming beneficial commensalE. colibiofilms.

scholarly journals Chinese herbal medicines and nutraceuticals inhibit Pseudomonas aeruginosa biofilm formation

2021 ◽  
Vol 3 (8) ◽  
Author(s):  
Minami Hayashi ◽  
Hiroshi Kaneko ◽  
Tetsuya Yamada ◽  
Hideaki Ikoshi ◽  
Norihisa Noguchi ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Type Species ◽  
Antimicrobial Agents ◽  
Herbal Medicines ◽  
Bacterial Strains ◽  
Chinese Herbal Medicines ◽  
Content Type ◽  
Chinese Herbal ◽  
Link Type

Pseudomonas aeruginosa is a major biofilm-forming, opportunistic pathogen. Tolerance to antimicrobial agents due to biofilm formation may lead to the emergence of antimicrobial-resistant bacterial strains. Thus, adjunctive agents that can inhibit biofilm formation are necessary to enhance the therapeutic efficacy of antimicrobial agents. In this study, we evaluated the anti-biofilm formation activity of selected Chinese herbal medicines and nutraceuticals, which are commercially available in Japan. Among the eight agents evaluated for their potential to inhibit biofilm formation, Eiekikaryu S, Iribakuga and Hyakujunro significantly reduced P. aeruginosa biofilm formation (P <0.05) without inhibiting bacterial growth. Additionally, the expression of biofilm-associated genes (rhlR, rhlA and lasB) in P. aeruginosa was significantly suppressed by Eiekikaryu S, Iribakuga and Hyakujunro (P <0.001). Our findings indicate that some Chinese herbal medicines and nutraceuticals can be potential adjunctive agents for antimicrobial therapy against P. aeruginosa .

scholarly journals Novel Strategy for Biofilm Inhibition by Using Small Molecules Targeting Molecular Chaperone DnaK

2014 ◽  
Vol 59 (1) ◽  
pp. 633-641 ◽  
Author(s):  
Ken-ichi Arita-Morioka ◽  
Kunitoshi Yamanaka ◽  
Yoshimitsu Mizunoe ◽  
Teru Ogura ◽  
Shinya Sugimoto
Keyword(s):  
Molecular Chaperone ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Dependent Manner ◽  
Cellular Functions ◽  
Biofilm Inhibition ◽  
Content Type ◽  
E Coli ◽  
Chaperone Dnak ◽  
Biofilm Development

ABSTRACTBiofilms are complex communities of microorganisms that attach to surfaces and are embedded in a self-produced extracellular matrix. Since these cells acquire increased tolerance against antimicrobial agents and host immune systems, biofilm-associated infectious diseases tend to become chronic. We show here that the molecular chaperone DnaK is important for biofilm formation and that chemical inhibition of DnaK cellular functions is effective in preventing biofilm development. Genetic, microbial, and microscopic analyses revealed that deletion of thednaKgene markedly reduced the production of the extracellular functional amyloid curli, which contributes to the robustness ofEscherichia colibiofilms. We tested the ability of DnaK inhibitors myricetin (Myr), telmisartan, pancuronium bromide, and zafirlukast to prevent biofilm formation ofE. coli. Only Myr, a flavonol widely distributed in plants, inhibited biofilm formation in a concentration-dependent manner (50% inhibitory concentration [IC50] = 46.2 μM); however, it did not affect growth. Transmission electron microscopy demonstrated that Myr inhibited the production of curli. Phenotypic analyses of thermosensitivity, cell division, intracellular level of RNA polymerase sigma factor RpoH, and vulnerability to vancomycin revealed that Myr altered the phenotype ofE. coliwild-type cells to make them resemble those of the isogenicdnaKdeletion mutant, indicating that Myr inhibits cellular functions of DnaK. These findings provide insights into the significance of DnaK in curli-dependent biofilm formation and indicate that DnaK is an ideal target for antibiofilm drugs.

scholarly journals Acetic Acid Acts as a Volatile Signal To Stimulate Bacterial Biofilm Formation

mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Yun Chen ◽  
Kevin Gozzi ◽  
Fang Yan ◽  
Yunrong Chai
Keyword(s):  
Acetic Acid ◽  
Bacillus Subtilis ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Bacterial Biofilm ◽  
Acetic Acid Production ◽  
Content Type ◽  
Metabolic Signal

ABSTRACTVolatiles are small air-transmittable chemicals with diverse biological activities. In this study, we showed that volatiles produced by the bacteriumBacillus subtilishad a profound effect on biofilm formation of neighboringB. subtiliscells that grew in proximity but were physically separated. We further demonstrated that one such volatile, acetic acid, is particularly potent in stimulating biofilm formation. Multiple lines of genetic evidence based onB. subtilismutants that are defective in either acetic acid production or transportation suggest thatB. subtilisuses acetic acid as a metabolic signal to coordinate the timing of biofilm formation. Lastly, we investigated howB. subtiliscells sense and respond to acetic acid in regulating biofilm formation. We showed the possible involvement of three sets of genes (ywbHG,ysbAB, andyxaKC), all encoding putative holin-antiholin-like proteins, in cells responding to acetic acid and stimulating biofilm formation. All three sets of genes were induced by acetate. A mutant with a triple mutation of those genes showed a severe delay in biofilm formation, whereas a strain overexpressingywbHGshowed early and robust biofilm formation. Results of our studies suggest thatB. subtilisand possibly other bacteria use acetic acid as a metabolic signal to regulate biofilm formation as well as a quorum-sensing-like airborne signal to coordinate the timing of biofilm formation by physically separated cells in the community.IMPORTANCEVolatiles are small, air-transmittable molecules produced by all kingdoms of organisms including bacteria. Volatiles possess diverse biological activities and play important roles in bacteria-bacteria and bacteria-host interactions. Although volatiles can be used as a novel and important way of cell-cell communication due to their air-transmittable nature, little is known about how the volatile-mediated signaling mechanism works. In this study, we demonstrate that the bacteriumBacillus subtilisuses one such volatile, acetic acid, as a quorum-sensing-like signal to coordinate the timing of the formation of structurally complex cell communities, also known as biofilms. We further characterized the molecular mechanisms of howB. subtilisresponds to acetic acid in stimulating biofilm formation. Our study also suggests that acetic acid may be used as a volatile signal for cross-species communication.

scholarly journals Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Mircea Radu Mihu ◽  
Vitor Cabral ◽  
Rodney Pattabhi ◽  
Moses T. Tar ◽  
Kelvin P. Davies ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Staphylococcus Aureus ◽  
Central Venous Catheter ◽  
Medical Devices ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Venous Catheter ◽  
Central Venous ◽  
Content Type ◽  
Nitric Oxide Releasing

ABSTRACT Staphylococcus aureus is frequently isolated in the setting of infections of indwelling medical devices, which are mediated by the microbe's ability to form biofilms on a variety of surfaces. Biofilm-embedded bacteria are more resistant to antimicrobial agents than their planktonic counterparts and often cause chronic infections and sepsis, particularly in patients with prolonged hospitalizations. In this study, we demonstrate that sustained nitric oxide-releasing nanoparticles (NO-np) interfere with S. aureus adhesion and prevent biofilm formation on a rat central venous catheter (CVC) model of infection. Confocal and scanning electron microscopy showed that NO-np-treated staphylococcal biofilms displayed considerably reduced thicknesses and bacterial numbers compared to those of control biofilms in vitro and in vivo, respectively. Although both phenotypes, planktonic and biofilm-associated staphylococci, of multiple clinical strains were susceptible to NO-np, bacteria within biofilms were more resistant to killing than their planktonic counterparts. Furthermore, chitosan, a biopolymer found in the exoskeleton of crustaceans and structurally integrated into the nanoparticles, seems to add considerable antimicrobial activity to the technology. Our findings suggest promising development and translational potential of NO-np for use as a prophylactic or therapeutic against bacterial biofilms on CVCs and other medical devices.

scholarly journals Assessment of Clofazimine and TB47 Combination Activity against Mycobacterium abscessus Using a Bioluminescent Approach

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Yang Liu ◽  
Yaoju Tan ◽  
M. Mahmudul Islam ◽  
Yuanyuan Cao ◽  
Xiaoyun Lu ◽  
...  
Keyword(s):  
Real Time ◽  
Antimicrobial Agents ◽  
Drug Efficacy ◽  
Mycobacterium Abscessus ◽  
New Drugs ◽  
Multiple Drug ◽  
Emerging Infections ◽  
Content Type

ABSTRACT Mycobacterium abscessus is intrinsically resistant to most antimicrobial agents. The emerging infections caused by M. abscessus and the lack of effective treatment call for rapid attention. Here, we intended to construct a selectable marker-free autoluminescent M. abscessus strain (designated UAlMab) as a real-time reporter strain to facilitate the discovery of effective drugs and regimens for treating M. abscessus. The UAlMab strain was constructed using the dif/Xer recombinase system. In vitro and in vivo activities of several drugs, including clofazimine and TB47, a recently reported cytochrome bc1 inhibitor, were assessed using UAlMab. Furthermore, the efficacy of multiple drug combinations, including the clofazimine and TB47 combination, were tested against 20 clinical M. abscessus isolates. The UAlMab strain enabled us to evaluate drug efficacy both in vitro and in live BALB/c mice in a real-time, noninvasive fashion. Importantly, although TB47 showed marginal activity either alone or in combination with clarithromycin, amikacin, or roxithromycin, the drug markedly potentiated the activity of clofazimine, both in vitro and in vivo. This study demonstrates that the use of the UAlMab strain can significantly facilitate rapid evaluation of new drugs and regimens. The clofazimine and TB47 combination is effective against M. abscessus, and dual/triple electron transport chain (ETC) targeting can be an effective therapeutic approach for treating mycobacterial infections.

scholarly journals Prevention and Treatment of Virulent Bacterial Biofilms with an Enzymatic Nitric Oxide-Releasing Dressing

2012 ◽  
Vol 56 (12) ◽  
pp. 6095-6103 ◽  
Author(s):  
Imran Sulemankhil ◽  
Jorge Gabriel Ganopolsky ◽  
Christopher Anthony Dieni ◽  
Andrei Florin Dan ◽  
Mitchell Lawrence Jones ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Medical Devices ◽  
Nosocomial Infections ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Bacterial Strains ◽  
Content Type ◽  
Prevention And Treatment ◽  
Complete Cell ◽  
Nitric Oxide Releasing

ABSTRACTThe use of percutaneous medical devices often results in nosocomial infections. Attachment of microorganisms to the surfaces of these medical devices triggers biofilm formation, which presents significant complications to the health of a patient and may lead to septicemia, thromboembolism, or endocarditis if not correctly treated. Although several antimicrobials are commonly used for prevention of biofilm formation, they have limited efficacy against formed biofilms. In this study, we report the use of an enzymatic, gaseous nitric oxide (gNO)-releasing dressing for the prevention and treatment ofAcinetobacter baumannii, methicillin-resistantStaphylococcus aureus, andPseudomonas aeruginosabiofilms. Results show that the bactericidal activity against biofilms of the test strains was dependent on time and rate of gNO release from the dressing. Following 6 h of treatment, gNO-releasing dressings significantly inhibited the growth of test strains relative to vehicle control dressings, demonstrating eradication of bacterial concentrations of up to 105CFU/cm2. Complete cell death was observed for both prevention of biofilm formation and treatment of 24-h-grown biofilms after 6 h of treatment with the gNO-releasing dressings. Further, gNO-releasing dressings were more efficient against formed biofilms than other antimicrobial agents currently used. These results demonstrate that the gNO-releasing dressing can produce sufficient levels of gNO over a therapeutically relevant duration for maximal bactericidal effects against virulent bacterial strains known to cause nosocomial infections.

scholarly journals Acetic Acid, the Active Component of Vinegar, Is an Effective Tuberculocidal Disinfectant

mBio ◽  
2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Claudia Cortesia ◽  
Catherine Vilchèze ◽  
Audrey Bernut ◽  
Whendy Contreras ◽  
Keyla Gómez ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Mycobacterium Tuberculosis ◽  
Nontuberculous Mycobacteria ◽  
Acetic Acid Solution ◽  
Multidrug Resistant ◽  
Mycobacterium Abscessus ◽  
Resistant Bacteria ◽  
Content Type ◽  
Poor Countries ◽  
Immunosuppressed Patients

ABSTRACT Effective and economical mycobactericidal disinfectants are needed to kill both Mycobacterium tuberculosis and non-M. tuberculosis mycobacteria. We found that acetic acid (vinegar) efficiently kills M. tuberculosis after 30 min of exposure to a 6% acetic acid solution. The activity is not due to pH alone, and propionic acid also appears to be bactericidal. M. bolletii and M. massiliense nontuberculous mycobacteria were more resistant, although a 30-min exposure to 10% acetic acid resulted in at least a 6-log10 reduction of viable bacteria. Acetic acid (vinegar) is an effective mycobactericidal disinfectant that should also be active against most other bacteria. These findings are consistent with and extend the results of studies performed in the early and mid-20th century on the disinfectant capacity of organic acids. IMPORTANCE Mycobacteria are best known for causing tuberculosis and leprosy, but infections with nontuberculous mycobacteria are an increasing problem after surgical or cosmetic procedures or in the lungs of cystic fibrosis and immunosuppressed patients. Killing mycobacteria is important because Mycobacterium tuberculosis strains can be multidrug resistant and therefore potentially fatal biohazards, and environmental mycobacteria must be thoroughly eliminated from surgical implements and respiratory equipment. Currently used mycobactericidal disinfectants can be toxic, unstable, and expensive. We fortuitously found that acetic acid kills mycobacteria and then showed that it is an effective mycobactericidal agent, even against the very resistant, clinically important Mycobacterium abscessus complex. Vinegar has been used for thousands of years as a common disinfectant, and if it can kill mycobacteria, the most disinfectant-resistant bacteria, it may prove to be a broadly effective, economical biocide with potential usefulness in health care settings and laboratories, especially in resource-poor countries.

scholarly journals Antimicrobial Treatment Provides a Competitive Advantage to Mycobacterium abscessus in a Dual-Species Biofilm with Pseudomonas aeruginosa

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Graciela Rodríguez-Sevilla ◽  
Aurélie Crabbé ◽  
Marta García-Coca ◽  
John Jairo Aguilera-Correa ◽  
Jaime Esteban ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Therapy ◽  
Biofilm Formation ◽  
Mycobacterium Abscessus ◽  
Antimicrobial Treatment ◽  
Physiological Factors ◽  
Content Type ◽  
Lung Infections ◽  
The Ideal

ABSTRACT The physiological factors that contribute to Mycobacterium abscessus lung infections remain unclear. We determined whether antibiotic treatment targeting a major cystic fibrosis pathogen (i.e., Pseudomonas aeruginosa) could provide the ideal conditions for the establishment of M. abscessus infection. Our data showed that P. aeruginosa inhibited M. abscessus biofilm formation under control conditions and that antimicrobial therapy selectively targeting P. aeruginosa diminished this competitive interaction, thereby increasing M. abscessus survival.

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