β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects

Glen, Karl A.; Lamont, Iain L.

doi:10.3390/pathogens10121638

Cited by 85 publications

(74 citation statements)

References 328 publications

(474 reference statements)

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“…As PGN is absent in most eukaryotes yet found in most bacteria, many successful antibiotics have targeted PGN; however, resistance to PGN-targeting antibiotics is on the rise (Magiorakos et al, 2012; Glen and Lamont, 2021). Structural information is needed to determine if pathogens modify PGN to avoid activating host detection and/or guard against PGN-targeting toxins and antibiotics.…”

Section: Introductionmentioning

confidence: 99%

Rickettsia typhi peptidoglycan mapping with data-dependent tandem mass spectrometry

Oyler

Rennoll-Bankert

Verhoeve

et al. 2022

Preprint

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Rickettsia species are diverse Gram-negative obligate intracellular bacteria often pervasive in numerous invertebrates, as well as fungal, nematode and microeukaryotic hosts. Certain species are etiological agents for well-known arthropod-borne illnesses; e.g., R. rickettsii (Rocky Mountain Spotted Fever), R. prowazekii (Epidemic Typhus), and R. typhi, (Endemic Typhus). Living freely in eukaryotic cytosol presumably exposes rickettsiae to host cell immune receptors, particularly those recognizing bacterial cell envelope glycoconjugates. However, the mechanics of host recognition of rickettsiae remain poorly defined. As rickettsiae synthesize a canonical Gram-negative cell envelope that includes peptidoglycan (PGN) and lipopolysaccharide (LPS), structural insight on these macromolecules is important for deciphering host responses to these pathogens. In this work, PGN from R. typhi was digested and the resultant subunits were analyzed by two different, albeit complementary, sample preparation methods. Both approaches were subsequently subjected to liquid chromatography/mass spectrometry analysis to infer PGN structure. R. typhi PGN was determined to be similar to most other Gram-negative bacteria, with mDAP-type muropeptide subunits. However, additional alanine residues were observed elongating the muropeptide stems, rather than the glycine residues usually observed in Gram-negative bacterial PGN. Despite this deviation, R. typhi contains a murein layer that is predicted to agonize host cellular PGN receptors and be susceptible to PGN-targeting antimicrobials. This same structure is likely synthesized by all Rickettsia species, as bioinformatics and comparative genomics analyses indicate the biosynthesis of PGN is highly conserved. Determining how host cells process this canonical glycoconjugate during infection is crucial for identifying factors behind rickettsial pathogenesis, including immunoavoidance or proinflammatory mechanisms possibly employed by rickettsiae with varying pathogenic potential.

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Section: Introductionmentioning

confidence: 99%

Rickettsia typhi peptidoglycan mapping with data-dependent tandem mass spectrometry

Oyler

Rennoll-Bankert

Verhoeve

et al. 2022

Preprint

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“…Since these changes occurred in both lineages, they likely happened prior to the emergence of the hypermutator lineage. MexR is a repressor of the MexAB-OprM efflux pump, and its disruption could lead to overexpression of MexAB-OprM, which has been linked to beta-lactam resistance (32). Likewise, the substitution in MexB has the potential to enhance efflux of beta-lactams.…”

Section: Resultsmentioning

confidence: 99%

“…Likewise, the substitution in MexB has the potential to enhance efflux of beta-lactams. Disruption of the OprD outer membrane porin contributes to high-level resistance to carbapenems (32). The hospital day 77 hypermutator isolates (but not the non-hypermutator lineage) also contained an arginine-to-histidine substitution at residue 504 of penicillin-binding protein 3, which may be responsible for the elevated MICs to aztreonam observed in this lineage (32).…”

Section: Resultsmentioning

confidence: 99%

“…Disruption of the OprD outer membrane porin contributes to high-level resistance to carbapenems (32). The hospital day 77 hypermutator isolates (but not the non-hypermutator lineage) also contained an arginine-to-histidine substitution at residue 504 of penicillin-binding protein 3, which may be responsible for the elevated MICs to aztreonam observed in this lineage (32). On hospital day 84, the hypermutator lineage acquired a threonine-to-isoleucine substitution in subunit A of DNA gyrase, which was associated with the development of resistance to ciprofloxacin and levofloxacin.…”

Section: Resultsmentioning

confidence: 99%

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Emergence of a Pseudomonas aeruginosa Hypermutator Strain During the Course of Ventilator-Associated Pneumonia

Nozick

Ozer

Kumar

et al. 2022

Preprint

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Hypermutator lineages of Pseudomonas aeruginosa arise frequently during the years of lung infection seen in patients with cystic fibrosis and bronchiectasis but are rare in the absence of structural lung disease. Since the onset of the COVID-19 pandemic, large numbers of patients have remained mechanically ventilated for extended periods of time. These patients are prone to acquire bacterial pathogens that persist for many weeks and have the opportunity to evolve within the pulmonary environment. However, little is known about what types of adaptations occur in these bacteria and whether these adaptations mimic those described in chronic infections. We describe a COVID-19 patient with a secondary Pseudomonas aeruginosa lung infection in which the causative bacterium persisted for >90 days. During the course of this infection, a hypermutator lineage of P. aeruginosa emerged and co-existed with a non-hypermutator lineage. Compared to the parental lineage, the hypermutator lineage evolved to be more extensively resistant to antibiotics, to change its type III secretion profile, and to grow more slowly. Genomic analyses of the hypermutator lineage identified numerous mutations, including in the mismatch repair gene mutL and other genes frequently mutated in individuals with cystic fibrosis. Together, these findings demonstrate that hypermutator phenotypes can emerge when clearance of P. aeruginosa fails to occur in typically acute infections such as ventilator-associated pneumonia and suggest that hypermutator lineages can affect patient treatments and outcomes.

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“…P. aeruginosa is known as one of the most important opportunistic bacterial pathogens found in many environments and leads to a high rate of deadly hospital-acquired infections ( Bahramian et al., 2019 ). The results of recent investigations have shown a high mortality rate for P. aeruginosa -associated infections mainly in patients with predisposing conditions such as cancer, cystic fibrosis, urinary tract infection, and burn wound infections ( Bahramian et al., 2019 ; Glen and Lamont, 2021 ). Different adhesion factors such as flagella, type IV pili, and biofilms cause adhesion and survivor of this bacterium on various surfaces, medical devices, and water ( Remold et al., 2011 ).…”

Section: Pseudomonasmentioning

confidence: 99%

PLGA-Based Nanoplatforms in Drug Delivery for Inhibition and Destruction of Microbial Biofilm

Shariati

Chegini

Ghaznavi‐Rad

et al. 2022

Front. Cell. Infect. Microbiol.

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The biofilm community of microorganisms has been identified as the dominant mode of microbial growth in nature and a common characteristic of different microorganisms such as Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis. The biofilm structure helps in the protection from environmental threats including host immune system and antimicrobial agents. Thus, the biofilm community has led to a higher prevalence of multidrug-resistant (MDR) strains in recent years. In this regard, the use of a new class of antibiotics, natural compounds, and anti-biofilm enzymes has been considered for the destruction of the microbial biofilm. However, different drawbacks such as low penetration, high susceptibility to degradation, instability, and poor solubility in aqueous solutions limit the use of anti-biofilm agents (ABAs) in a clinical setting. As such, recent studies have been using poly lactic-co-glycolic acid (PLGA)-based nanoplatforms (PLGA NPFs) for delivery of ABAs that have reported promising results. These particles, due to proper drug loading and release kinetics, could suppress microbial attachment, colonization, and biofilm formation for a long time. Additionally, PLGA NPFs, because of the high drug-loading efficiencies, hydrophilic surface, negative charge, and electrostatic interaction, lead to effective penetration of antibiotics to the deeper layer of the biofilm, thereby eliminating the microbial biofilm. Thus, PLGA NPFs could be considered as a potential candidate for coating catheters and other medical material surfaces for inhibition and destruction of the microbial biofilm. However, the exact interaction of PLGA NPFs and the microbial biofilm should be evaluated in animal studies. Additionally, a future goal will be to develop PLGA formulations as systems that can be used for the treatment of the MDR microbial biofilm, since the exact interactions of PLGA NPFs and these biofilm structures are not elucidated. In the present review article, we have discussed various aspects of PLGA usage for inhibition and destruction of the microbial biofilm along with different methods and procedures that have been used for improving PLGA NPF efficacy against the microbial biofilm.

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β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects

Cited by 85 publications

References 328 publications

Rickettsia typhi peptidoglycan mapping with data-dependent tandem mass spectrometry

Rickettsia typhi peptidoglycan mapping with data-dependent tandem mass spectrometry

Emergence of a Pseudomonas aeruginosa Hypermutator Strain During the Course of Ventilator-Associated Pneumonia

PLGA-Based Nanoplatforms in Drug Delivery for Inhibition and Destruction of Microbial Biofilm

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