New Sequence Type ST3449 in Multidrug-Resistant Pseudomonas aeruginosa Isolates from a Cystic Fibrosis Patient

Pseudomonas aeruginosa is one of the most critical bacterial pathogens associated with chronic infections in cystic fibrosis patients. Here we show the phenotypic and genotypic characterization of five consecutive multidrug-resistant isolates of P. aeruginosa collected during a month from a CF patient with end-stage lung disease and fatal outcome. The isolates exhibited distinct colony morphologies and pigmentation and differences in their capacity to produce biofilm and virulence potential evaluated in larvae of Galleria mellonella. Whole genome-sequencing showed that isolates belonged to a novel sequence type ST3449 and serotype O6. Analysis of their resistome demonstrated the presence of genes blaOXA-396, blaPAO, aph(3’)-IIb, catB, crpP and fosA and new mutations in chromosomal genes conferring resistance to different antipseudomonal antibiotics. Genes exoS, exoT, exoY, toxA, lasI, rhlI and tse1 were among the 220 virulence genes detected. The different phenotypic and genotypic features found reveal the adaptation of clone ST3449 to the CF lung environment by a number of mutations affecting genes related with biofilm formation, quorum sensing and antimicrobial resistance. Most of these mutations are commonly found in CF isolates, which may give us important clues for future development of new drug targets to combat P. aeruginosa chronic infections.

Download Full-text

In Vitro Newly Isolated Environmental Phage Activity against Biofilms Preformed by Pseudomonas aeruginosa from Patients with Cystic Fibrosis

Microorganisms ◽

10.3390/microorganisms9030478 ◽

2021 ◽

Vol 9 (3) ◽

pp. 478

Author(s):

Ersilia Vita Fiscarelli ◽

Martina Rossitto ◽

Paola Rosati ◽

Nour Essa ◽

Valentina Crocetta ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Multidrug Resistant ◽

In Vitro Test ◽

Chronic Infections ◽

Hospital Environments ◽

Vitro Test ◽

General Reliability ◽

Phage Activity

As disease worsens in patients with cystic fibrosis (CF), Pseudomonas aeruginosa (PA) colonizes the lungs, causing pulmonary failure and mortality. Progressively, PA forms typical biofilms, and antibiotic treatments determine multidrug-resistant (MDR) PA strains. To advance new therapies against MDR PA, research has reappraised bacteriophages (phages), viruses naturally infecting bacteria. Because few in vitro studies have tested phages on CF PA biofilms, general reliability remains unclear. This study aimed to test in vitro newly isolated environmental phage activity against PA isolates from patients with CF at Bambino Gesù Children’s Hospital (OBG), Rome, Italy. After testing in vitro phage activities, we combined phages with amikacin, meropenem, and tobramycin against CF PA pre-formed biofilms. We also investigated new emerging morphotypes and bacterial regrowth. We obtained 22 newly isolated phages from various environments, including OBG. In about 94% of 32 CF PA isolates tested, these phages showed in vitro PA lysis. Despite poor efficacy against chronic CF PA, five selected-lytic-phages (Φ4_ZP1, Φ9_ZP2, Φ14_OBG, Φ17_OBG, and Φ19_OBG) showed wide host activity. The Φ4_ZP1-meropenem and Φ14_OBG-tobramycin combinations significantly reduced CF PA biofilms (p < 0.001). To advance potential combined phage-antibiotic therapy, we envisage further in vitro test combinations with newly isolated phages, including those from hospital environments, against CF PA biofilms from early and chronic infections.

Download Full-text

Antimicrobial Susceptibility of Pseudomonas aeruginosa Isolated from Cystic Fibrosis Patients in Northern Europe

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01046-16 ◽

2016 ◽

Vol 60 (11) ◽

pp. 6735-6741 ◽

Cited By ~ 24

Author(s):

Muhammad-Hariri Mustafa ◽

Hussein Chalhoub ◽

Olivier Denis ◽

Ariane Deplano ◽

Anne Vergison ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Multidrug Resistant ◽

Sequence Type ◽

Content Type ◽

The United Kingdom ◽

Genes Encoding ◽

Control Criteria ◽

Susceptibility Profiles ◽

And Control

ABSTRACTPseudomonas aeruginosais a major cause of morbidity and mortality in cystic fibrosis patients. This study compared the antimicrobial susceptibilities of 153P. aeruginosaisolates from the United Kingdom (UK) (n =58), Belgium (n =44), and Germany (n =51) collected from 118 patients during routine visits over the period from 2006 to 2012. MICs were measured by broth microdilution. Genes encoding extended-spectrum β-lactamases (ESBL), metallo-β-lactamases, and carbapenemases were detected by PCR. Pulsed-field gel electrophoresis and multilocus sequence typing were performed on isolates resistant to ≥3 antibiotic classes among the penicillins/cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and polymyxins. Based on EUCAST/CLSI breakpoints, susceptibility rates were ≤30%/≤40% (penicillins, ceftazidime, amikacin, and ciprofloxacin), 44 to 48%/48 to 63% (carbapenems), 72%/72% (tobramycin), and 92%/78% (colistin) independent of patient age. Sixty percent of strains were multidrug resistant (MDR; European Centre for Disease Prevention and Control criteria). Genes encoding the most prevalent ESBL (BEL, PER, GES, VEB, CTX-M, TEM, SHV, and OXA), metallo-β-lactamases (VIM, IMP, and NDM), or carbapenemases (OXA-48 and KPC) were not detected. The Liverpool epidemic strain (LES) was prevalent in UK isolates only (75% of MDR isolates). Four MDR sequence type 958 (ST958) isolates were found to be spread over the three countries. The other MDR clones were evidenced in ≤3 isolates and localized in a single country. A new sequence type (ST2254) was discovered in one MDR isolate in Germany. Clonal and nonclonal isolates with different susceptibility profiles were found in 20 patients. Thus, resistance and MDR are highly prevalent in routine isolates from 3 countries, with meropenem, tobramycin, and colistin remaining the most active drugs.

Download Full-text

MexXY efflux pump overexpression and aminoglycoside resistance in cystic fibrosis isolates of Pseudomonas aeruginosa from chronic infections

Canadian Journal of Microbiology ◽

10.1139/cjm-2017-0380 ◽

2017 ◽

Vol 63 (12) ◽

pp. 929-938 ◽

Cited By ~ 8

Author(s):

Manu Singh ◽

Yvonne C.W. Yau ◽

Shirley Wang ◽

Valerie Waters ◽

Ayush Kumar

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Efflux Pump ◽

Multidrug Resistant ◽

Regulatory Genes ◽

Multidrug Efflux ◽

Chronic Infections ◽

Aminoglycoside Resistance ◽

Resistance Nodulation Division ◽

Lung Infections

In this study, we analyzed 15 multidrug-resistant cystic fibrosis isolates of Pseudomonas aeruginosa from chronic lung infections for expression of 4 different multidrug efflux systems (MexAB–OprM, MexCD–OprJ, MexEF–OprN, and MexXY), using quantitative reverse transcriptase PCR. Overexpression of MexXY pump was observed in all of the isolates tested. Analysis of regulatory genes that control the expression of these 4 efflux pumps revealed a number of previously uncharacterized mutations. Our work shows that MexXY pump overexpression is common in cystic fibrosis isolates and could be contributing to their reduced aminoglycoside susceptibility. Further, we also identified novel mutations in the regulatory genes of the 4 abovementioned Resistance–Nodulation–Division superfamily pumps that may be involved in the overexpression of these pumps.

Download Full-text

Genomic Analysis of Carbapenem-Resistant Pseudomonas aeruginosa Isolated From Urban Rivers Confirms Spread of Clone Sequence Type 277 Carrying Broad Resistome and Virulome Beyond the Hospital

Frontiers in Microbiology ◽

10.3389/fmicb.2021.701921 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fernanda Esposito ◽

Brenda Cardoso ◽

Herrison Fontana ◽

Bruna Fuga ◽

Adriana Cardenas-Arias ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Galleria Mellonella ◽

Genomic Analysis ◽

Bioinformatic Analysis ◽

Environmental Water ◽

Multidrug Resistant ◽

Sequence Type ◽

Infection Model ◽

Urban Rivers ◽

Secretion Systems

The dissemination of antibiotic-resistant priority pathogens beyond hospital settings is both a public health and an environmental problem. In this regard, high-risk clones exhibiting a multidrug-resistant (MDR) or extensively drug-resistant (XDR) phenotype have shown rapid adaptation at the human-animal-environment interface. In this study, we report genomic data and the virulence potential of the carbapenemase, São Paulo metallo-β-lactamase (SPM-1)-producing Pseudomonas aeruginosa strains (Pa19 and Pa151) isolated from polluted urban rivers, in Brazil. Bioinformatic analysis revealed a wide resistome to clinically relevant antibiotics (carbapenems, aminoglycosides, fosfomycin, sulfonamides, phenicols, and fluoroquinolones), biocides (quaternary ammonium compounds) and heavy metals (copper), whereas the presence of exotoxin A, alginate, quorum sensing, types II, III, and IV secretion systems, colicin, and pyocin encoding virulence genes was associated with a highly virulent behavior in the Galleria mellonella infection model. These results confirm the spread of healthcare-associated critical-priority P. aeruginosa belonging to the MDR sequence type 277 (ST277) clone beyond the hospital, highlighting that the presence of these pathogens in environmental water samples can have clinical implications for humans and other animals.

Download Full-text

Pseudomonas aeruginosa PA14 Enhances the Efficacy of Norfloxacin against Staphylococcus aureus Newman Biofilms

Journal of Bacteriology ◽

10.1128/jb.00159-20 ◽

2020 ◽

Vol 202 (18) ◽

Cited By ~ 1

Author(s):

Giulia Orazi ◽

Fabrice Jean-Pierre ◽

George A. O’Toole

Keyword(s):

Cystic Fibrosis ◽

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Antimicrobial Agents ◽

Respiratory Infections ◽

Multiple Infection ◽

Bacterial Biofilms ◽

Interspecies Interactions ◽

Chronic Infections ◽

Content Type

ABSTRACT The thick mucus within the airways of individuals with cystic fibrosis (CF) promotes frequent respiratory infections that are often polymicrobial. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent pathogens that cause CF pulmonary infections, and both are among the most common etiologic agents of chronic wound infections. Furthermore, the ability of P. aeruginosa and S. aureus to form biofilms promotes the establishment of chronic infections that are often difficult to eradicate using antimicrobial agents. In this study, we found that multiple LasR-regulated exoproducts of P. aeruginosa, including 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), siderophores, phenazines, and rhamnolipids, likely contribute to the ability of P. aeruginosa PA14 to shift S. aureus Newman norfloxacin susceptibility profiles. Here, we observe that exposure to P. aeruginosa exoproducts leads to an increase in intracellular norfloxacin accumulation by S. aureus. We previously showed that P. aeruginosa supernatant dissipates the S. aureus membrane potential, and furthermore, depletion of the S. aureus proton motive force recapitulates the effect of the P. aeruginosa PA14 supernatant on shifting norfloxacin sensitivity profiles of biofilm-grown S. aureus Newman. From these results, we hypothesize that exposure to P. aeruginosa PA14 exoproducts leads to increased uptake of the drug and/or an impaired ability of S. aureus Newman to efflux norfloxacin. Surprisingly, the effect observed here of P. aeruginosa PA14 exoproducts on S. aureus Newman susceptibility to norfloxacin seemed to be specific to these strains and this antibiotic. Our results illustrate that microbially derived products can alter the ability of antimicrobial agents to kill bacterial biofilms. IMPORTANCE Pseudomonas aeruginosa and Staphylococcus aureus are frequently coisolated from multiple infection sites, including the lungs of individuals with cystic fibrosis (CF) and nonhealing diabetic foot ulcers. Coinfection with P. aeruginosa and S. aureus has been shown to produce worse outcomes compared to infection with either organism alone. Furthermore, the ability of these pathogens to form biofilms enables them to cause persistent infection and withstand antimicrobial therapy. In this study, we found that P. aeruginosa-secreted products dramatically increase the ability of the antibiotic norfloxacin to kill S. aureus biofilms. Understanding how interspecies interactions alter the antibiotic susceptibility of bacterial biofilms may inform treatment decisions and inspire the development of new therapeutic strategies.

Download Full-text

1458. Uncharted territories: applying “precision medicine” to understand the treacherous landscape of extensively and multidrug resistant (XDR and MDR) Pseudomonas aeruginosa in a patient with cystic fibrosis and lung transplantation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1639 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S731-S731

Author(s):

Laura J Rojas ◽

Mohamad Yasmin ◽

Jacquelynn Benjamino ◽

Steven Marshall ◽

Kailynn DeRonde ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Lung Transplantation ◽

Precision Medicine ◽

Clinical Sample ◽

Phylogenetic Reconstruction ◽

Multidrug Resistant ◽

Population Diversity ◽

Before And After ◽

Research Grant

Abstract Background Pseudomonas aeruginosa is a persistent and difficult-to-treat pathogen in many patients, especially those with cystic fibrosis (CF). Herein, we describe our experience managing a young woman suffering from CF with XDR P. aeruginosa who underwent lung transplantation. We highlight the contemporary difficulties reconciling the clinical, microbiological, and genetic information. Methods Mechanism-based-susceptibility disk diffusion synergy testing with double and triple antibiotic combinations aided in choosing tailored antimicrobial combinations to control the infection in the pre-transplant period, create an effective perioperative prophylaxis regimen, and manage recurrent infections in the post-transplant period. Thirty-six sequential XDR and PDR P. aeruginosa isolates obtained from the patient within a 17-month period, before and after a double-lung transplant were analyzed by whole genome sequencing (WGS) and RNAseq in order to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence changes over time Results Our phylogenetic reconstruction demonstrates that these isolates represent a genotypically and phenotypically heterogeneous population. The pattern of mutation accumulation and variation of gene expression suggests that a group of closely related strains was present in the patient prior to transplantation and continued to evolve throughout the course of treatment regardless of antibiotic usage.Our findings challenge antimicrobial stewardship programs that assist with the selection and duration of antibiotic regimens in critically ill and immunocompromised patients based on single-isolate laboratory-derived resistant profiles. We propose that an approach sampling the population of pathogens present in a clinical sample instead of single colonies be applied instead when dealing with XDR P. aeruginosa, especially in patients with CF. Conclusion In complex cases such as this, real-time combination testing and genomic/transcriptomic data could lead to the application of true “precision medicine” by helping clinicians choose the combination antimicrobial therapy most likely to be successful against a population of MDR pathogens present. Disclosures Federico Perez, MD, MS, Accelerate (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support) Robert A. Bonomo, MD, Entasis, Merck, Venatorx (Research Grant or Support)

Download Full-text

Pseudomonas aeruginosa PAO 1 In Vitro Time–Kill Kinetics Using Single Phages and Phage Formulations—Modulating Death, Adaptation, and Resistance

Antibiotics ◽

10.3390/antibiotics10070877 ◽

2021 ◽

Vol 10 (7) ◽

pp. 877

Author(s):

Ana Mafalda Pinto ◽

Alberta Faustino ◽

Lorenzo M. Pastrana ◽

Manuel Bañobre-López ◽

Sanna Sillankorva

Keyword(s):

Pseudomonas Aeruginosa ◽

Phage Therapy ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Chronic Infections ◽

Swarming Motility ◽

Resistance Development ◽

Healthcare Settings ◽

Time Kill

Pseudomonas aeruginosa is responsible for nosocomial and chronic infections in healthcare settings. The major challenge in treating P. aeruginosa-related diseases is its remarkable capacity for antibiotic resistance development. Bacteriophage (phage) therapy is regarded as a possible alternative that has, for years, attracted attention for fighting multidrug-resistant infections. In this work, we characterized five phages showing different lytic spectrums towards clinical isolates. Two of these phages were isolated from the Russian Microgen Sextaphage formulation and belong to the Phikmvviruses, while three Pbunaviruses were isolated from sewage. Different phage formulations for the treatment of P. aeruginosa PAO1 resulted in diversified time–kill outcomes. The best result was obtained with a formulation with all phages, prompting a lower frequency of resistant variants and considerable alterations in cell motility, resulting in a loss of 73.7% in swimming motility and a 79% change in swarming motility. These alterations diminished the virulence of the phage-resisting phenotypes but promoted their growth since most became insensitive to a single or even all phages. However, not all combinations drove to enhanced cell killings due to the competition and loss of receptors. This study highlights that more caution is needed when developing cocktail formulations to maximize phage therapy efficacy. Selecting phages for formulations should consider the emergence of phage-resistant bacteria and whether the formulations are intended for short-term or extended antibacterial application.

Download Full-text

Within-Host Evolution of Pseudomonas aeruginosa Reveals Adaptation toward Iron Acquisition from Hemoglobin

mBio ◽

10.1128/mbio.00966-14 ◽

2014 ◽

Vol 5 (3) ◽

Cited By ~ 88

Author(s):

Rasmus Lykke Marvig ◽

Søren Damkiær ◽

S. M. Hossein Khademi ◽

Trine M. Markussen ◽

Søren Molin ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Iron Acquisition ◽

Chronic Infections ◽

Content Type ◽

Mortality And Morbidity ◽

Airway Infections ◽

Host Evolution ◽

Promoter Mutations

ABSTRACTPseudomonas aeruginosaairway infections are a major cause of mortality and morbidity of cystic fibrosis (CF) patients. In order to persist,P. aeruginosadepends on acquiring iron from its host, and multiple different iron acquisition systems may be active during infection. This includes the pyoverdine siderophore and thePseudomonasheme utilization (phu) system. While the regulation and mechanisms of several iron-scavenging systems are well described, it is not clear whether such systems are targets for selection during adaptation ofP. aeruginosato the host environment. Here we investigated the within-host evolution of the transmissibleP. aeruginosaDK2 lineage. We found positive selection for promoter mutations leading to increased expression of thephusystem. By mimicking conditions of the CF airwaysin vitro, we experimentally demonstrate that increased expression ofphuRconfers a growth advantage in the presence of hemoglobin, thus suggesting thatP. aeruginosaevolves toward iron acquisition from hemoglobin. To rule out that this adaptive trait is specific to the DK2 lineage, we inspected the genomes of additionalP. aeruginosalineages isolated from CF airways and found similar adaptive evolution in two distinct lineages (DK1 and PA clone C). Furthermore, in all three lineages,phuRpromoter mutations coincided with the loss of pyoverdine production, suggesting that within-host adaptation toward heme utilization is triggered by the loss of pyoverdine production. Targeting heme utilization might therefore be a promising strategy for the treatment ofP. aeruginosainfections in CF patients.IMPORTANCEMost bacterial pathogens depend on scavenging iron within their hosts, which makes the battle for iron between pathogens and hosts a hallmark of infection. Accordingly, the ability of the opportunistic pathogenPseudomonas aeruginosato cause chronic infections in cystic fibrosis (CF) patients also depends on iron-scavenging systems. While the regulation and mechanisms of several such iron-scavenging systems have been well described, not much is known about how the within-host selection pressures act on the pathogens’ ability to acquire iron. Here, we investigated the within-host evolution ofP. aeruginosa, and we found evidence thatP. aeruginosaduring long-term infections evolves toward iron acquisition from hemoglobin. This adaptive strategy might be due to a selective loss of other iron-scavenging mechanisms and/or an increase in the availability of hemoglobin at the site of infection. This information is relevant to the design of novel CF therapeutics and the development of models of chronic CF infections.

Download Full-text

Carbapenem-Resistant Klebsiella pneumoniae Clinical Isolates: In Vivo Virulence Assessment in Galleria mellonella and Potential Therapeutics by Polycationic Oligoethyleneimine

Antibiotics ◽

10.3390/antibiotics10010056 ◽

2021 ◽

Vol 10 (1) ◽

pp. 56

Author(s):

Dalila Mil-Homens ◽

Maria Martins ◽

José Barbosa ◽

Gabriel Serafim ◽

Maria J. Sarmento ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Galleria Mellonella ◽

Multidrug Resistant ◽

In Vitro Models ◽

Clinical Isolates ◽

In Vivo Model ◽

Virulence Potential ◽

Hospital Acquired

Klebsiella pneumoniae, one of the most common pathogens found in hospital-acquired infections, is often resistant to multiple antibiotics. In fact, multidrug-resistant (MDR) K. pneumoniae producing KPC or OXA-48-like carbapenemases are recognized as a serious global health threat. In this sense, we evaluated the virulence of K. pneumoniae KPC(+) or OXA-48(+) aiming at potential antimicrobial therapeutics. K. pneumoniae carbapenemase (KPC) and the expanded-spectrum oxacillinase OXA-48 isolates were obtained from patients treated in medical care units in Lisbon, Portugal. The virulence potential of the K. pneumonia clinical isolates was tested using the Galleria mellonella model. For that, G. mellonella larvae were inoculated using patients KPC(+) and OXA-48(+) isolates. Using this in vivo model, the KPC(+) K. pneumoniae isolates showed to be, on average, more virulent than OXA-48(+). Virulence was found attenuated when a low bacterial inoculum (one magnitude lower) was tested. In addition, we also report the use of a synthetic polycationic oligomer (L-OEI-h) as a potential antimicrobial agent to fight infectious diseases caused by MDR bacteria. L-OEI-h has a broad-spectrum antibacterial activity and exerts a significantly bactericidal activity within the first 5-30 min treatment, causing lysis of the cytoplasmic membrane. Importantly, the polycationic oligomer showed low toxicity against in vitro models and no visible cytotoxicity (measured by survival and health index) was noted on the in vivo model (G. mellonella), thus L-OEI-h is foreseen as a promising polymer therapeutic for the treatment of MDR K. pneumoniae infections.

Download Full-text

Heterogenous response to R-pyocin killing in populations of Pseudomonas aeruginosa sourced from cystic fibrosis lungs

10.1101/2020.08.05.238956 ◽

2020 ◽

Author(s):

Madeline Mei ◽

Jacob Thomas ◽

Stephen P. Diggle

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Genotypic Diversity ◽

Opportunistic Pathogen ◽

Chronic Infections ◽

Bacterial Populations ◽

Heterogeneous Populations ◽

Lung Infections ◽

The Impact ◽

Lps Binding

AbstractBacteriocins are proteinaceous antimicrobials produced by bacteria which are active against other strains of the same species. R-type pyocins are phage tail-like bacteriocins produced by Pseudomonas aeruginosa. Due to their anti-pseudomonal activity, R-pyocins have potential as therapeutics in infection. P. aeruginosa is a Gram-negative opportunistic pathogen and is particularly problematic for individuals with cystic fibrosis (CF). P. aeruginosa from CF lung infections develop increasing resistance to antibiotics, making new treatment approaches essential. P. aeruginosa populations become phenotypically and genotypically diverse during infection, however little is known of the efficacy of R-pyocins against heterogeneous populations. R-pyocins vary by subtype (R1-R5), distinguished by binding to different residues on the lipopolysaccharide (LPS). Each type varies in killing spectrum, and each strain produces only one R-type. To evaluate the prevalence of different R-types, we screened P. aeruginosa strains from the International Pseudomonas Consortium Database (IPCD) and from our biobank of CF strains. We found that (i) R1-types were the most prevalent R-type among strains from respiratory sources and (ii) isolates collected from the same patient have the same R-type. We then assessed the impact of diversity on R-pyocin susceptibility and found a heterogenous response to R-pyocins within populations, likely due to differences in the LPS core. Our work reveals that heterogeneous populations of microbes exhibit variable susceptibility to R-pyocins and highlights that there is likely heterogeneity in response to other types of LPS-binding antimicrobials, including phage.ImportanceR-pyocins have potential as alternative therapeutics against Pseudomonas aeruginosa in chronic infection, however little is known about the efficacy of R-pyocins in heterogeneous bacterial populations. P. aeruginosa is known to become resistant to multiple antibiotics, as well as evolve phenotypic and genotypic diversity over time; thus it is particularly difficult to eradicate in chronic cystic fibrosis (CF) lung infections. In this study, we found that P. aeruginosa populations from CF lungs maintain the same R-pyocin genotype but exhibit heterogeneity in susceptibility to R-pyocins from other strains. Our findings suggest there is likely heterogeneity in response to other types of LPS-binding antimicrobials, such as phage, highlighting the necessity of further studying the potential of LPS-binding antimicrobial particles as alternative therapies in chronic infections.

Download Full-text