scholarly journals Mycobacterium abscessusCells Have Altered Antibiotic Tolerance and Surface Glycolipids in Artificial Cystic Fibrosis Sputum Medium

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
Augusto Cesar Hunt-Serracin ◽  
Brian J. Parks ◽  
Joseph Boll ◽  
Cara C. Boutte
Keyword(s):  
Cystic Fibrosis ◽  
Multidrug Resistant ◽  
Mycobacterium Abscessus ◽  
Cell Physiology ◽  
Antibiotic Tolerance ◽  
Planktonic Cells ◽  
Content Type ◽  
Cystic Fibrosis Sputum ◽  
Poor Treatment ◽  
Nutrient Conditions

ABSTRACTMycobacterium abscessusis a biofilm-forming, multidrug-resistant nontuberculous mycobacterial (NTM) pathogen increasingly found in cystic fibrosis patients. Antibiotic treatment for these infections is often unsuccessful, partly due toM. abscessus’s high intrinsic antibiotic resistance. It is not clear whether antibiotic tolerance caused by biofilm formation also contributes to poor treatment outcomes. We studied the surface glycolipids and antibiotic tolerance ofM. abscessusbiofilms grown in artificial cystic fibrosis sputum (ACFS) medium to determine how they are affected by nutrient conditions that mimic infection. We found thatM. abscessusdisplays more of the virulence lipid trehalose dimycolate when grown in ACFS than when grown in standard lab medium. In ACFS medium, biofilm-associated cells were more antibiotic tolerant than planktonic cells in the same well. This contrasts with standard lab media, where both biofilm and planktonic cells are highly antibiotic tolerant. These results indicate thatM. abscessuscell physiology in biofilms depends on environmental factors and that nutrient conditions found within cystic fibrosis infections could contribute to both increased virulence and antibiotic tolerance.

scholarly journals Biofilm-associatedMycobacterium abscessuscells have altered antibiotic tolerance and surface glycolipids in Artificial Cystic Fibrosis Sputum Media

2018 ◽  
Author(s):  
Augusto Cesar Hunt-Serracin ◽  
Brian J. Parks ◽  
Joseph Boll ◽  
Cara Boutte
Keyword(s):  
Cystic Fibrosis ◽  
Biofilm Formation ◽  
Mycobacterium Abscessus ◽  
Cell Physiology ◽  
Antibiotic Tolerance ◽  
Planktonic Cells ◽  
Cystic Fibrosis Sputum ◽  
Trehalose Dimycolate ◽  
Poor Treatment ◽  
Nutrient Conditions

AbstractMycobacterium abscessus(Mab) is a biofilm-forming, multi-drug resistant, non-tuberculous mycobacterial (NTM) pathogen increasingly found in Cystic Fibrosis patients. Antibiotic treatment for these infections is often unsuccessful, partly due toMab’s high intrinsic antibiotic resistance. It is not clear whether antibiotic tolerance caused by biofilm formation also contributes to poor treatment outcomes. We studied the surface glycolipids and antibiotic tolerance ofMabbiofilms grown in Artificial Cystic Fibrosis Sputum (ACFS) media in order to determine how they are affected by nutrient conditions that mimic infection. We found thatMabdisplays more of the virulence lipid trehalose dimycolate when grown in ACFS compared to standard lab media. In ACFS media, biofilm-associated cells are more antibiotic tolerant than planktonic cells in the same well. This contrasts with standard lab medias, where biofilm and planktonic cells are both highly antibiotic tolerant. These results indicate thatMabcell physiology in biofilms depends on environmental factors, and that nutrient conditions found within Cystic Fibrosis infections could contribute to both increased virulence and antibiotic tolerance.

scholarly journals Draft Genome Sequence of the Multidrug-Resistant Strain Pseudomonas aeruginosa PA291, Isolated from Cystic Fibrosis Sputum

2021 ◽  
Vol 10 (36) ◽  
Author(s):  
Tiffany Luong ◽  
Ashley Schumann ◽  
Douglas Conrad ◽  
Dwayne Roach
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Genome Sequence ◽  
Resistant Strain ◽  
De Novo ◽  
Draft Genome ◽  
Multidrug Resistant ◽  
Content Type ◽  
Cystic Fibrosis Sputum ◽  
Multidrug Resistant Strain

Here, we report the genome sequence of PA291, a nonmucoid, multidrug-resistant strain of Pseudomonas aeruginosa isolated from cystic fibrosis sputum. Short reads were de novo assembled into 190 contigs and scaffold assembled to a length of 6.26 Mbp. PhiSpy predicts that PA291 is free of prophages.

scholarly journals Whole-Genome Sequences of Mycobacterium abscessus subsp. massiliense Isolates from Brazil

2021 ◽  
Vol 10 (28) ◽  
Author(s):  
Edson Machado ◽  
Fernanda Cristina Oliveira ◽  
Rafael Silva Duarte ◽  
Ana Carolina Carvalho ◽  
Pedro Henrique Campanini Cândido ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Cystic Fibrosis Patient ◽  
Multidrug Resistant ◽  
Mycobacterium Abscessus ◽  
Whole Genome ◽  
Genome Sequences ◽  
Genome Composition ◽  
Content Type ◽  
Severe Infections

The Mycobacterium abscessus complex comprises multidrug-resistant, opportunistic, and rapidly growing pathogens responsible for severe infections. Here, we report the genome composition of four Mycobacterium abscessus subsp. massiliense isolates from three sources: two from the lung of a cystic fibrosis patient, one from a mammary cyst, and one from a gutter system.

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 Characterization of RelA in Acinetobacter baumannii

2020 ◽  
Vol 202 (12) ◽  
Author(s):  
María Pérez-Varela ◽  
Aimee R. P. Tierney ◽  
Ju-Sim Kim ◽  
Andrés Vázquez-Torres ◽  
Philip Rather
Keyword(s):  
Acinetobacter Baumannii ◽  
Galleria Mellonella ◽  
Multidrug Resistant ◽  
Cell Physiology ◽  
Content Type ◽  
Content Model ◽  
Transposon Insertion ◽  
Downstream Effectors

ABSTRACT In response to nutrient depletion, the RelA and SpoT proteins generate the signaling molecule (p)ppGpp, which then controls a number of downstream effectors to modulate cell physiology. In Acinetobacter baumannii strain AB5075, a relA ortholog (ABUW_3302) was identified by a transposon insertion that conferred an unusual colony phenotype. An in-frame deletion in relA (ΔrelA) failed to produce detectable levels of ppGpp when amino acid starvation was induced with serine hydroxamate. The ΔrelA mutant was blocked from switching from the virulent opaque colony variant (VIR-O) to the avirulent translucent colony variant (AV-T), but the rate of AV-T to VIR-O switching was unchanged. In addition, the ΔrelA mutation resulted in a pronounced hypermotile phenotype on 0.35% agar plates. This hypermotility was dependent on the activation of a LysR regulator ABUW_1132, which was required for expression of AbaR, a LuxR family quorum-sensing regulator. In the ΔrelA mutant, ABUW_1132 was also required for the increased expression of an operon composed of the ABUW_3766-ABUW_3773 genes required for production of the surfactant-like lipopeptide acinetin 505. Additional phenotypes identified in the ΔrelA mutant included (i) cell elongation at high density, (ii) reduced formation of persister cells tolerant to colistin and rifampin, and (iii) decreased virulence in a Galleria mellonella model. IMPORTANCE Acinetobacter baumannii is a pathogen of worldwide importance. Due to the increasing prevalence of antibiotic resistance, these infections are becoming increasingly difficult to treat. New therapies are required to combat multidrug-resistant isolates. The role of RelA in A. baumannii is largely unknown. This study demonstrates that like in other bacteria, RelA controls a variety of functions, including virulence. Strategies to inhibit the activity of RelA and the resulting production of ppGpp could inhibit virulence and may represent a new therapeutic approach.

scholarly journals Rifabutin Acts in Synergy and Is Bactericidal with FrontlineMycobacterium abscessusAntibiotics Clarithromycin and Tigecycline, Suggesting a Potent Treatment Combination

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Mark Pryjma ◽  
Ján Burian ◽  
Charles J. Thompson
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Mycobacterium Abscessus ◽  
Triple Combination ◽  
Pulmonary Infections ◽  
Treatment Combination ◽  
Content Type ◽  
Current Treatment Regimen ◽  
Drug Regimens

ABSTRACTMycobacterium abscessusis a rapidly emerging mycobacterial pathogen causing dangerous pulmonary infections. Because these bacteria are intrinsically multidrug resistant, treatment options are limited and have questionable efficacy. The current treatment regimen relies on a combination of antibiotics, including clarithromycin paired with amikacin and either imipenem or cefoxitin. Tigecycline may be added when triple therapy is ineffective. We initially screened a library containing the majority of clinically available antibiotics for anti-M. abscessusactivity. The screen identified rifabutin, which was then investigated for its interactions withM. abscessusantibiotics used in drug regimens. Combination of rifabutin with either clarithromycin or tigecycline generated synergistic anti-M. abscessusactivity, dropping the rifabutin MIC below concentrations found in the lung. Importantly, these combinations generated bactericidal activity. The triple combination of clarithromycin, tigecycline, and rifabutin was also synergistic, and clinically relevant concentrations had a sterilizing effect onM. abscessuscultures. We suggest that combinations including rifabutin should be further investigated for treatment ofM. abscessuspulmonary infections.

scholarly journals Biofilm Compared to Conventional Antimicrobial Susceptibility of Stenotrophomonas maltophilia Isolates from Cystic Fibrosis Patients

2013 ◽  
Vol 57 (3) ◽  
pp. 1546-1548 ◽  
Author(s):  
Kitty Wu ◽  
Yvonne C. W. Yau ◽  
Larissa Matukas ◽  
Valerie Waters
Keyword(s):  
Cystic Fibrosis ◽  
Antimicrobial Susceptibility ◽  
Stenotrophomonas Maltophilia ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Resistant Organism ◽  
High Dose ◽  
Content Type

ABSTRACTStenotrophomonas maltophiliais a multidrug-resistant organism increasingly isolated from the lungs of cystic fibrosis (CF) patients. One hundred twenty-fiveS. maltophiliaisolates from 85 CF patients underwent planktonic and biofilm susceptibility testing against 9 different antibiotics, alone and in double antibiotic combinations. WhenS. maltophiliaisolates were grown as a biofilm, 4 of the 10 most effective antibiotic combinations included high-dose levofloxacin and 7 of the 10 combinations included colistin at doses achievable by aerosolization.

scholarly journals In Vitro Activities of β-Lactam–β-Lactamase Inhibitor Antimicrobial Agents against Cystic Fibrosis Respiratory Pathogens

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
Lindsay J. Caverly ◽  
Theodore Spilker ◽  
Linda M. Kalikin ◽  
Terri Stillwell ◽  
Carol Young ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Respiratory Pathogens ◽  
Content Type ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Increased Activity ◽  
Lactamase Inhibitor

ABSTRACT We tested the in vitro activities of ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, piperacillin-tazobactam, and 11 other antimicrobial agents against 420 Burkholderia, Achromobacter, Stenotrophomonas, and Pandoraea strains, 89% of which were cultured from respiratory specimens from persons with cystic fibrosis. Among the β-lactam–β-lactamase inhibitor agents, meropenem-vaborbactam had the greatest activity against Burkholderia and Achromobacter, including multidrug-resistant and extensively-drug-resistant strains. None of the newer β-lactam–β-lactamase combination drugs showed increased activity compared to that of the older agents against Stenotrophomonas maltophilia or Pandoraea spp.

scholarly journals Antibacterial Effects of Phage Lysin LysGH15 on Planktonic Cells and Biofilms of Diverse Staphylococci

2018 ◽  
Vol 84 (15) ◽  
Author(s):  
Yufeng Zhang ◽  
Mengjun Cheng ◽  
Hao Zhang ◽  
Jiaxin Dai ◽  
Zhimin Guo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Multidrug Resistant ◽  
Planktonic Cells ◽  
Content Type ◽  
Resistant Strains ◽  
Staphylococcus Hominis ◽  
Phage Lysin

ABSTRACT Treatment of infections caused by staphylococci has become more difficult because of the emergence of multidrug-resistant strains as well as biofilm formation. In this study, we observed the ability of the phage lysin LysGH15 to eliminate staphylococcal planktonic cells and biofilms formed by Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus hominis. All these strains were sensitive to LysGH15, showing reductions in bacterial counts of approximately 4 log units within 30 min after treatment with 20 μg/ml of LysGH15, and the MICs ranged from 8 μg/ml to 32 μg/ml. LysGH15 efficiently prevented biofilm formation by the four staphylococcal species at a dose of 50 μg/ml. At a higher dose (100 μg/ml), LysGH15 also showed notable disrupting activity against 24-h and 72-h biofilms formed by S. aureus and coagulase-negative species. In the in vivo experiments, a single intraperitoneal injection of LysGH15 (20 μg/mouse) administered 1 h after the injection of S. epidermidis at double the minimum lethal dose was sufficient to protect the mice. The S. epidermidis cell counts were 4 log units lower in the blood and 3 log units lower in the organs of mice 24 h after treatment with LysGH15 than in the untreated control mice. LysGH15 reduced cytokine levels in the blood and improved pathological changes in the organs. The broad antistaphylococcal activity exerted by LysGH15 on planktonic cells and biofilms makes LysGH15 a valuable treatment option for biofilm-related or non-biofilm-related staphylococcal infections. IMPORTANCE Most staphylococcal species are major causes of health care- and community-associated infections. In particular, Staphylococcus aureus is a common and dangerous pathogen, and Staphylococcus epidermidis is a ubiquitous skin commensal and opportunistic pathogen. Treatment of infections caused by staphylococci has become more difficult because of the emergence of multidrug-resistant strains as well as biofilm formation. In this study, we found that all tested S. aureus, S. epidermidis, Staphylococcus haemolyticus, and Staphylococcus hominis strains were sensitive to the phage lysin LysGH15 (MICs ranging from 8 to 32 μg/ml). More importantly, LysGH15 not only prevented biofilm formation by these staphylococci but also disrupted 24-h and 72-h biofilms. Furthermore, the in vivo efficacy of LysGH15 was demonstrated in a mouse model of S. epidermidis bacteremia. Thus, LysGH15 exhibits therapeutic potential for treating biofilm-related or non-biofilm-related infections caused by diverse staphylococci.

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