Inhibition of Virulence Factors and Biofilm Formation of Acinetobacter Baumannii by Naturally-derived and Synthetic Drugs

2020 ◽  
Vol 21 ◽  
Author(s):  
Nilushi Indika Bamunuar Achchi ◽  
Fazlurrahman Khan ◽  
Young-Mog Kim

: Acinetobacter baumannii is a Gram-negative, aerobic, non-motile, and pleomorphic bacillus. A. baumanii is also a highly-infectious pathogen causing high mortality and morbidity rates in intensive care units. The discovery of novel agents against A. baumanii infections is urgently needed due to the emergence of drug-resistant A. baumannii strains and the limited number of efficacious antibiotics available for treatment. In addition to the production of several virulence factors, A. baumannii forms biofilms on the host cell surface as well. Formation of biofilms occurs through initial surface attachment, microcolony formation, biofilm maturation, and detachment stages, and is one of the major drug resistance mechanisms employed by A. baumanii. Several studies have previously reported the efficacy of naturally-derived and synthetic compounds as anti-biofilm and anti-virulence agents against A. baumannii. Here, inhibition of biofilm formation and virulence factors of A. baumannii using naturally-derived and synthetic compounds are reviewed.

Author(s):  
María-Guadalupe Avila-Novoa ◽  
Oscar-Alberto Solís-Velázquez ◽  
Daniel-Eduardo Rangel-López ◽  
Jean-Pierre González-Gómez ◽  
Pedro-Javier Guerrero-Medina ◽  
...  

Acinetobacter baumannii is an important opportunistic pathogen that shows resistance to cephalosporins, penicillins, carbapenems, fluoroquinolones, and aminoglycosides, the multiresistance being associated with its ability to form biofilms in clinical environments. The aim of this study was to determine biofilm formation and its potential association with genes involved in antibiotic resistance mechanisms of A. baumannii isolates of different clinical specimens. We demonstrated 100% of the A. baumannii isolates examined to be multidrug resistant (MDR), presenting a 73.3% susceptibility to cefepime and a 53.3% susceptibility to ciprofloxacin. All A. baumannii isolates were positive for blaOXA-51, 33.3% being positive for blaOXA-23 and ISAba1, and 73.3% being positive for gyrA. We found 86.6% of A. baumannii strains to be low-grade biofilm formers and 13.3% to be biofilm negative; culturing on Congo red agar (CRA) plates revealed that 73.3% of the A. baumannii isolates to be biofilm producers, while 26.6% were not. These properties, combined with the role of A. baumannii as a nosocomial pathogen, increase the probability of A. baumannii causing nosocomial infections and outbreaks as a complication during therapeutic treatments and emphasize the need to control A. baumannii biofilms in hospital environments.


Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 119 ◽  
Author(s):  
Carole Ayoub Moubareck ◽  
Dalal Hammoudi Halat

Being a multidrug-resistant and an invasive pathogen, Acinetobacter baumannii is one of the major causes of nosocomial infections in the current healthcare system. It has been recognized as an agent of pneumonia, septicemia, meningitis, urinary tract and wound infections, and is associated with high mortality. Pathogenesis in A. baumannii infections is an outcome of multiple virulence factors, including porins, capsules, and cell wall lipopolysaccharide, enzymes, biofilm production, motility, and iron-acquisition systems, among others. Such virulence factors help the organism to resist stressful environmental conditions and enable development of severe infections. Parallel to increased prevalence of infections caused by A. baumannii, challenging and diverse resistance mechanisms in this pathogen are well recognized, with major classes of antibiotics becoming minimally effective. Through a wide array of antibiotic-hydrolyzing enzymes, efflux pump changes, impermeability, and antibiotic target mutations, A. baumannii models a unique ability to maintain a multidrug-resistant phenotype, further complicating treatment. Understanding mechanisms behind diseases, virulence, and resistance acquisition are central to infectious disease knowledge about A. baumannii. The aims of this review are to highlight infections and disease-producing factors in A. baumannii and to touch base on mechanisms of resistance to various antibiotic classes.


2018 ◽  
Vol 4 (3) ◽  
pp. 88 ◽  
Author(s):  
Emma Camacho ◽  
Arturo Casadevall

Several species in the genus Cryptococcus are facultative intracellular pathogens capable of causing disease associated with high mortality and morbidity in humans. These fungi interact with other organisms in the soil, and these interactions may contribute to the development of adaptation mechanisms that function in virulence by promoting fungal survival in animal hosts. Fungal adhesion molecules, also known as adhesins, have been classically considered as cell-surface or secreted proteins that play critical roles in microbial pathogenesis or in biofilm formation as structural components. Pathogenic Cryptococcus spp. differ from other pathogenic yeasts in having a polysaccharide capsule that covers the cell wall surface and precludes interactions of those structures with host cell receptors. Hence, pathogenic Cryptococcus spp. use unconventional tools for surface attachment. In this essay, we review the unique traits and mechanisms favoring adhesion of Cryptococcus spp. to biotic and abiotic surfaces. Knowledge of the traits that mediate adherence could be exploited in the development of therapeutic, biomedical, and/or industrial products.


2016 ◽  
Vol 19 (1) ◽  
pp. 16-21 ◽  
Author(s):  
Cristina Anca Tudor ◽  
◽  
Cristian Boros ◽  
Raluca Petre ◽  
Adriana Elena Nica ◽  
...  

Acinetobacter baumannii is a bacterium that is commonly causes of nosocomial infections, the most common site of infection and colonization is the lower respiratory tract. Although it is present more often in immunocompromised patients, the defense mechanism against infection with Acinetobacter baumanii remains incomplete elucidated. Among the virulence factors involved in infection with Acinetobacter baumanii are production and release of exopolysaccharide, and ability to biofilm formation in tissues. Understanding of virulence mechanisms is important for early initiation of treatment.


Nano LIFE ◽  
2012 ◽  
Vol 02 (04) ◽  
pp. 1242004 ◽  
Author(s):  
JOHN F. LING ◽  
MARY V. GRAHAM ◽  
NATHANIEL C. CADY

Bacterial pathogens, such as Pseudomonas aeruginosa, readily form biofilms on surfaces, limiting the efficacy of antimicrobial and antibiotic treatments. To mitigate biofilm formation, surfaces are often treated with antimicrobial agents, which have limited lifetime and efficacy. Recent studies have shown that well-ordered topographic patterns can limit bacterial attachment to surfaces and limit biofilm formation. In this study, nano and microscale patterned poly(dimethylsiloxane) surfaces were evaluated for their ability to affect adhesion and biofilm formation by Pseudomonas aeruginosa. Feature size and spacing were varied from 500 nm to 2 μm and included repeating arrays of square pillars, holes, lines and biomimetc Sharklet™ patterns. Bacterial surface adhesion and biofilm formation was assessed in microfluidic flow devices and under static conditions. Attachment profiles under static and fluid flow varied within topography types, sizes and spacing. Pillar structures of all sizes yielded lower surface attachment than line-based patterns and arrays of holes. This trend was also observed for biomimetic Sharklet™ patterns, with reduced bacterial attachment to "raised" features as compared to "recessed" features. Notably, none of the topographically patterned surfaces outperformed smooth surfaces (without topography) for resisting cell adhesion. Initial surface attachment patterns were indicative of subsequent biofilm formation and coverage, suggesting a direct role of surface topography in biofilm-based biofouling.


Microbiology ◽  
2003 ◽  
Vol 149 (12) ◽  
pp. 3473-3484 ◽  
Author(s):  
Andrew P. Tomaras ◽  
Caleb W. Dorsey ◽  
Richard E. Edelmann ◽  
Luis A. Actis

Acinetobacter baumannii causes severe infections in compromised patients, survives on abiotic surfaces in hospital environments and colonizes different medical devices. In this study the analysis of the processes involved in surface attachment and biofilm formation by the prototype strain 19606 was initiated. This strain attaches to and forms biofilm structures on plastic and glass surfaces, particularly at the liquid–air interface of cultures incubated stagnantly. The cell aggregates, which contain cell stacks separated by water channels, formed under different culture conditions and were significantly enhanced under iron limitation. Electron and fluorescence microscopy showed that pili and exopolysaccharides are part of the cell aggregates formed by this strain. Electron microscopy of two insertion derivatives deficient in attachment and biofilm formation revealed the disappearance of pili-like structures and DNA sequencing analysis showed that the transposon insertions interrupted genes with the highest similarity to hypothetical genes found in Pseudomonas aeruginosa, Pseudomonas putida and Vibrio parahaemolyticus. Although the products of these genes, which have been named csuC and csuE, have no known functions, they are located within a polycistronic operon that includes four other genes, two of which encode proteins related to chaperones and ushers involved in pili assembly in other bacteria. Introduction of a copy of the csuE parental gene restored the adherence phenotype and the presence of pili on the cell surface of the csuE mutant, but not that of the csuC derivative. These results demonstrate that the expression of a chaperone-usher secretion system, some of whose components appear to be acquired from unrelated sources, is required for pili formation and the concomitant attachment to plastic surfaces and the ensuing formation of biofilms by A. baumannii cells.


2019 ◽  
Author(s):  
Carly Ching ◽  
Paul Muller ◽  
Merlin Brychcy ◽  
Alicyn Reverdy ◽  
Brian Nguyen ◽  
...  

AbstractInfections caused by Acinetobacter baumannii, a Gram-negative opportunistic pathogen, are difficult to eradicate due to the bacterium’s propensity to quickly gain antibiotic resistances and form protective bacterial multicellular communities known as biofilms. The A. baumannii DNA damage response (DDR) mediates antibiotic resistance acquisition and regulates RecA in an atypical fashion; both RecALow and RecAHigh cell types are formed in response to DNA damage. In this study, we show that RecA levels modulate biofilm development, formation and dispersal, through bfmR, the global biofilm regulator. RecA loss results in surface attachment and prominent biofilms while elevated RecA leads to diminished attachment and dispersal. Recalcitrance to treatment may be explained by DDR induction, common during infection, and the balance between biofilm maintenance in low RecA cells, and increased mutagenesis and dispersal to reach new niches in high RecA cells. These data highlight the importance of understanding fundamental biology to better treat bacterial infections.ImpactThe mechanism of biofilm formation and dispersal in A. baumannii, shown here to depend on RecA levels, contributes to the understanding of recalcitrant infections caused by this important pathogen.


Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1548
Author(s):  
Libardo Suárez ◽  
Andrés Pereira ◽  
William Hidalgo ◽  
Nelson Uribe

Staphylococcus aureus is an important etiological agent that causes skin infections, and has the propensity to form biofilms, leading to significant mortality and morbidity in patients with wounds. Mucus secretion from the Giant African snail Achatina fulica is a potential source of biologically active substances that might be an important source for new drugs to treat resistant and biofilm-forming bacteria such as S. aureus. This study evaluated the effect of semi-purified fractions from the mucus secretion of A. fulica on the growth, biofilm formation and virulence factors of S. aureus. Two fractions: FMA30 (Mw >30 kDa) and FME30 (Mw 30−10 kDa) exhibited antimicrobial activity against S. aureus with a MIC50 of 25 and 125 µg/mL, respectively. An inhibition of biofilm formation higher than 80% was observed at 9 µg/mL with FMA30 and 120 µg/mL with FME30. Furthermore, inhibition of hemolytic and protease activity was determined using a concentration of MIC20, and FME30 showed a strong inhibitory effect in the formation of clots. We report for the first time the effect of semi-purified fractions of mucus secretion of A. fulica on biofilm formation and activity of virulence factors such as α-hemolysin, coagulase and proteases produced by S. aureus strains.


2007 ◽  
Vol 189 (12) ◽  
pp. 4418-4424 ◽  
Author(s):  
Katherine P. Lemon ◽  
Darren E. Higgins ◽  
Roberto Kolter

ABSTRACT The food-borne pathogen Listeria monocytogenes attaches to environmental surfaces and forms biofilms that can be a source of food contamination, yet little is known about the molecular mechanisms of its biofilm development. We observed that nonmotile mutants were defective in biofilm formation. To investigate how flagella might function during biofilm formation, we compared the wild type with flagellum-minus and paralyzed-flagellum mutants. Both nonmotile mutants were defective in biofilm development, presumably at an early stage, as they were also defective in attachment to glass during the first few hours of surface exposure. This attachment defect could be significantly overcome by providing exogenous movement toward the surface via centrifugation. However, this centrifugation did not restore mature biofilm formation. Our results indicate that it is flagellum-mediated motility that is critical for both initial surface attachment and subsequent biofilm formation. Also, any role for L. monocytogenes flagella as adhesins on abiotic surfaces appears to be either minimal or motility dependent under the conditions we examined.


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