scholarly journals Broad-spectrum adaptive antibiotic resistance associated with Pseudomonas aeruginosa mucin-dependent surfing motility

2018 ◽  
Author(s):  
Evelyn Sun ◽  
Erin E. Gill ◽  
Reza Falsafi ◽  
Amy Yeung ◽  
Sijie Liu ◽  
...  

AbstractSurfing motility is a novel form of surface adaptation exhibited by the nosocomial pathogen, Pseudomonas aeruginosa, in the presence of the glycoprotein mucin that is found in high abundance at mucosal surfaces especially the lungs of cystic fibrosis and bronchiectasis patients. Here we investigated the adaptive antibiotic resistance of P. aeruginosa under conditions in which surfing occurs compared to cells undergoing swimming. P. aeruginosa surfing cells were significantly more resistant to several classes of antibiotics including aminoglycosides, carbapenems, polymyxins, and fluroquinolones. This was confirmed by incorporation of antibiotics into growth medium, which revealed a concentration-dependent inhibition of surfing motility that occurred at concentrations much higher than those needed to inhibit swimming. To investigate the basis of resistance, RNA-Seq was performed and revealed that surfing influenced the expression of numerous genes. Included amongst genes dysregulated under surfing conditions were multiple genes from the Pseudomonas resistome, which are known to affect antibiotic resistance when mutated. Screening transposon mutants in these surfing-dysregulated resistome genes revealed that several of these mutants exhibited changes in susceptibility to one or more antibiotics under surfing conditions, consistent with a contribution to the observed adaptive resistance. In particular, several mutants in resistome genes, including armR, recG, atpB, clpS, nuoB, and certain hypothetical genes such as PA5130, PA3576 and PA4292, showed contributions to broad-spectrum resistance under surfing conditions and could be complemented by their respective cloned genes. Therefore, we propose that surfing adaption led to extensive multidrug adaptive resistance as a result of the collective dysregulation of diverse genes.


2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Evelyn Sun ◽  
Erin E. Gill ◽  
Reza Falsafi ◽  
Amy Yeung ◽  
Sijie Liu ◽  
...  

ABSTRACT Surfing motility is a novel form of surface adaptation exhibited by the nosocomial pathogen Pseudomonas aeruginosa in the presence of the glycoprotein mucin, which is found in high abundance at mucosal surfaces, especially those of the lungs of cystic fibrosis and bronchiectasis patients. Here, we investigated the adaptive antibiotic resistance of P. aeruginosa under conditions in which surfing occurs compared that in to cells undergoing swimming. P. aeruginosa surfing cells were significantly more resistant to several classes of antibiotics, including aminoglycosides, carbapenems, polymyxins, and fluoroquinolones. This was confirmed by incorporation of antibiotics into growth medium, which revealed a concentration-dependent inhibition of surfing motility that occurred at concentrations much higher than those needed to inhibit swimming. To investigate the basis of resistance, transcriptome sequencing (RNA-Seq) was performed and revealed that surfing influenced the expression of numerous genes. Included among genes dysregulated under surfing conditions were multiple genes from the Pseudomonas resistome; these genes are known to affect antibiotic resistance when mutated. Screening transposon mutants in these surfing-dysregulated resistome genes revealed that several of these mutants exhibited changes in susceptibility to one or more antibiotics under surfing conditions, consistent with a contribution to the observed adaptive resistance. In particular, several mutants in resistome genes, including armR, recG, atpB, clpS, nuoB, and certain hypothetical genes, such as PA5130, PA3576, and PA4292, showed contributions to broad-spectrum resistance under surfing conditions and could be complemented by their respective cloned genes. Therefore, we propose that surfing adaption led to extensive multidrug adaptive resistance as a result of the collective dysregulation of diverse genes.



2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Shannon R. Coleman ◽  
Travis Blimkie ◽  
Reza Falsafi ◽  
Robert E. W. Hancock

ABSTRACT Swarming surface motility is a complex adaptation leading to multidrug antibiotic resistance and virulence factor production in Pseudomonas aeruginosa. Here, we expanded previous studies to demonstrate that under swarming conditions, P. aeruginosa PA14 is more resistant to multiple antibiotics, including aminoglycosides, β-lactams, chloramphenicol, ciprofloxacin, tetracycline, trimethoprim, and macrolides, than swimming cells, but is not more resistant to polymyxin B. We investigated the mechanism(s) of swarming-mediated antibiotic resistance by examining the transcriptomes of swarming cells and swarming cells treated with tobramycin by transcriptomics (RNA-Seq) and reverse transcriptase quantitative PCR (qRT-PCR). RNA-Seq of swarming cells (versus swimming) revealed 1,581 dysregulated genes, including 104 transcriptional regulators, two-component systems, and sigma factors, numerous upregulated virulence and iron acquisition factors, and downregulated ribosomal genes. Strain PA14 mutants in resistome genes that were dysregulated under swarming conditions were tested for their ability to swarm in the presence of tobramycin. In total, 41 mutants in genes dysregulated under swarming conditions were shown to be more resistant to tobramycin under swarming conditions, indicating that swarming-mediated tobramycin resistance was multideterminant. Focusing on two genes downregulated under swarming conditions, both prtN and wbpW mutants were more resistant to tobramycin, while the prtN mutant was additionally resistant to trimethoprim under swarming conditions; complementation of these mutants restored susceptibility. RNA-Seq of swarming cells treated with subinhibitory concentrations of tobramycin revealed the upregulation of the multidrug efflux pump MexXY and downregulation of virulence factors.



2018 ◽  
Vol 200 (23) ◽  
Author(s):  
Evelyn Sun ◽  
Sijie Liu ◽  
Robert E. W. Hancock

ABSTRACTBacterial rapid surfing motility is a novel surface adaptation ofPseudomonas aeruginosain the presence of the glycoprotein mucin. Here, we show that other Gram-negative motile bacterial species, includingEscherichia coli,Salmonella enterica,Vibrio harveyi,Enterobacter cloacae, andProteus mirabilis, also exhibit the physical characteristics of surfing on the surface of agar plates containing 0.4% mucin, where surfing motility was generally more rapid and less dependent on medium viscosity than was swimming motility. As previously observed inPseudomonas aeruginosa, all surfing species exhibited some level of broad-spectrum adaptive resistance, although the antibiotics to which they demonstrated surfing-mediated resistance differed. Surfing motility inP. aeruginosawas found to be dependent on the quorum-sensing systems of this organism; however, this aspect was not conserved in other tested bacterial species, includingV. harveyiandS. enterica, as demonstrated by assaying specific quorum-sensing mutants. Thus, rapid surfing motility is a complex surface growth adaptation that is conserved in several motile bacteria, involves flagella, and leads to diverse broad-spectrum antibiotic resistance, but it is distinct in terms of dependence on quorum sensing.IMPORTANCEThis study showed for the first time that surfing motility, a novel form of surface motility first discovered inPseudomonas aeruginosaunder artificial cystic fibrosis conditions, including the presence of high mucin content, is conserved in other motile bacterial species known to be mucosa-associated, includingEscherichia coli,Salmonella enterica, andProteus mirabilis. Here, we demonstrated that key characteristics of surfing, including the ability to adapt to various viscous environments and multidrug adaptive resistance, are also conserved. Using mutagenesis assays, we also identified the importance of all three known quorum-sensing systems, Las, Rhl, and Pqs, inP. aeruginosain regulating surfing motility, and we also observed a conserved dependence of surfing on flagella in certain species.



Author(s):  
Ana Maravić ◽  
Ivica Šamanić ◽  
Matilda Šprung ◽  
Željana Fredotović ◽  
Nada Ilić ◽  
...  


2018 ◽  
Vol 54 (99) ◽  
pp. 13929-13932 ◽  
Author(s):  
Max Purro ◽  
Jing Qiao ◽  
Zhi Liu ◽  
Morgan Ashcraft ◽  
May P. Xiong

The outer membrane ofPseudomonas aeruginosafunctions primarily as a permeability barrier and imparts a broad spectrum of intrinsic antibiotic resistance.



2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Hussein A Kadhum ◽  
Thualfakar H Hasan2

The study involved the selection of two isolates from Bacillus subtilis to investigate their inhibitory activity against some bacterial pathogens. B sub-bacteria were found to have a broad spectrum against test bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. They were about 23-30 mm and less against Klebsiella sp. The sensitivity of some antibodies was tested on the test samples. The results showed that the inhibitory ability of bacterial growth in the test samples using B. subtilis extract was more effective than the antibiotics used.



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