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Frontiers in Cellular and Infection... 2023Polymicrobial infections include various microorganisms, often necessitating different treatment methods than a monomicrobial infection. Scientists have been puzzled by... (Review)
Review
Polymicrobial infections include various microorganisms, often necessitating different treatment methods than a monomicrobial infection. Scientists have been puzzled by the complex interactions within these communities for generations. The presence of specific microorganisms warrants a chronic infection and impacts crucial factors such as virulence and antibiotic susceptibility. Game theory is valuable for scenarios involving multiple decision-makers, but its relevance to polymicrobial infections is limited. Eco-evolutionary dynamics introduce causation for multiple proteomic interactions like metabolic syntropy and niche segregation. The review culminates both these giants to form evolutionary dynamics (ED). There is a significant amount of literature on inter-bacterial interactions that remain unsynchronised. Such raw data can only be moulded by analysing the ED involved. The review culminates the inter-bacterial interactions in multiple clinically relevant polymicrobial infections like chronic wounds, CAUTI, otitis media and dental carries. The data is further moulded with ED to analyse the niche colonisation of two notoriously competitive bacteria: and . The review attempts to develop a future trajectory for polymicrobial research by following recent innovative strategies incorporating ED to curb polymicrobial infections.
Topics: Humans; Coinfection; Proteomics; Staphylococcus aureus; Bacteria; Virulence; Pseudomonas aeruginosa
PubMed: 38145044
DOI: 10.3389/fcimb.2023.1295063 -
Respiratory Research Nov 2023The prevalence and clinical correlates of antibiotic resistance genes (ARGs) in bronchiectasis are not entirely clear. We aimed to profile the ARGs in sputum from adults...
The prevalence and clinical correlates of antibiotic resistance genes (ARGs) in bronchiectasis are not entirely clear. We aimed to profile the ARGs in sputum from adults with bronchiectasis, and explore the association with airway microbiome and disease severity and subtypes. In this longitudinal study, we prospectively collected 118 sputum samples from stable and exacerbation visits of 82 bronchiectasis patients and 19 healthy subjects. We profiled ARGs with shotgun metagenomic sequencing, and linked these to sputum microbiome and clinical characteristics, followed by validation in an international cohort. We compared ARG profiles in bronchiectasis according to disease severity, blood and sputum inflammatory subtypes. Unsupervised clustering revealed a Pseudomonas predominant subgroup (n = 16), Haemophilus predominant subgroup (n = 48), and balanced microbiome subgroup (N = 54). ARGs of multi-drug resistance were over-dominant in the Pseudomonas-predominant subgroup, while ARGs of beta-lactam resistance were most abundant in the Haemophilus-predominant subgroup. Pseudomonas-predominant subgroup yielded the highest ARG diversity and total abundance, while Haemophilus-predominant subgroup and balanced microbiota subgroup were lowest in ARG diversity and total abundance. PBP-1A, ksgA and emrB (multidrug) were most significantly enriched in Haemophilus-predominant subtype. ARGs generally correlated positively with Bronchiectasis Severity Index, fluoroquinolone use, and modified Reiff score. 68.6% of the ARG-clinical correlations could be validated in an independent international cohort. In conclusion, ARGs are differentially associated with the dominant microbiome and clinical characteristics in bronchiectasis.
Topics: Adult; Humans; Haemophilus; Pseudomonas; Longitudinal Studies; Bronchiectasis; Respiratory System; Anti-Bacterial Agents
PubMed: 37919749
DOI: 10.1186/s12931-023-02562-8 -
Nature Communications Sep 2023Chronic infection with the bacterial pathogen Pseudomonas aeruginosa often leads to coexistence of heterogeneous populations carrying diverse mutations. In particular,...
Chronic infection with the bacterial pathogen Pseudomonas aeruginosa often leads to coexistence of heterogeneous populations carrying diverse mutations. In particular, loss-of-function mutations affecting the quorum-sensing regulator LasR are often found in bacteria isolated from patients with lung chronic infection and cystic fibrosis. Here, we study the evolutionary dynamics of polymorphic P. aeruginosa populations using isolates longitudinally collected from patients with chronic obstructive pulmonary disease (COPD). We find that isolates deficient in production of different sharable extracellular products are sequentially selected in COPD airways, and lasR mutants appear to be selected first due to their quorum-sensing defects. Polymorphic populations including lasR mutants display survival advantages in animal models of infection and modulate immune responses. Our study sheds light on the multistage evolution of P. aeruginosa populations during their adaptation to host lungs.
Topics: Animals; Humans; Pseudomonas aeruginosa; Persistent Infection; Pulmonary Disease, Chronic Obstructive; Cystic Fibrosis; Lung
PubMed: 37749088
DOI: 10.1038/s41467-023-41704-w -
BioDrugs : Clinical Immunotherapeutics,... Sep 2023Multidrug-resistant (MDR) bacteria are considered a health threat worldwide, and this problem is set to increase over the decades. The ESKAPE, a group of six pathogens... (Review)
Review
Multidrug-resistant (MDR) bacteria are considered a health threat worldwide, and this problem is set to increase over the decades. The ESKAPE, a group of six pathogens including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. is the major source of concern due to their high death incidence and nosocomial acquired infection. Host defence peptides (HDPs) are a class of ribosomally synthesised peptides that have shown promising results in combating MDR, including the ESKAPE group, in- and outside bacterial biofilms. However, their poor pharmacokinetics in physiological mediums may impede HDPs from becoming viable clinical candidates. To circumvent this problem, chemical engineering of HDPs has been seen as an emergent approach to not only improve their pharmacokinetics but also their efficacy against pathogens. In this review, we explore several chemical modifications of HDPs that have shown promising results, especially against ESKAPE pathogens, and provide an overview of the current findings with respect to each modification.
Topics: Humans; Antimicrobial Cationic Peptides; Klebsiella pneumoniae; Enterobacter; Pseudomonas aeruginosa; Enterococcus faecium; Anti-Bacterial Agents
PubMed: 37300748
DOI: 10.1007/s40259-023-00608-3 -
ACS Infectious Diseases Jul 2023Traditional antibacterial screens rely on growing bacteria in nutrient-replete conditions which are not representative of the natural environment or sites of infection....
Traditional antibacterial screens rely on growing bacteria in nutrient-replete conditions which are not representative of the natural environment or sites of infection. Instead, screening in more physiologically relevant conditions may reveal novel activity for existing antibiotics. Here, we screened a panel of antibiotics reported to lack activity against the opportunistic Gram-negative bacterium, , under low-nutrient and low-iron conditions, and discovered that the glycopeptide vancomycin inhibited the growth of at low micromolar concentrations through its canonical mechanism of action, disruption of peptidoglycan crosslinking. Spontaneous vancomycin-resistant mutants underwent activating mutations in the sensor kinase of the two-component CpxSR system, which induced cross-resistance to almost all classes of β-lactams, including the siderophore antibiotic cefiderocol. Other mutations that conferred vancomycin resistance mapped to WapR, an α-1,3-rhamnosyltransferase involved in lipopolysaccharide core biosynthesis. A WapR P164T mutant had a modified LPS profile compared to wild type that was accompanied by increased susceptibility to select bacteriophages. We conclude that screening in nutrient-limited conditions can reveal novel activity for existing antibiotics and lead to discovery of new and impactful resistance mechanisms.
Topics: Vancomycin; Pseudomonas aeruginosa; Anti-Bacterial Agents; Glycopeptides; Nutrients
PubMed: 37279282
DOI: 10.1021/acsinfecdis.3c00167 -
BMC Microbiology Jul 2023Microorganisms that activate plant immune responses are useful for application as biocontrol agents in agriculture to minimize crop losses. The present study was...
BACKGROUND
Microorganisms that activate plant immune responses are useful for application as biocontrol agents in agriculture to minimize crop losses. The present study was conducted to identify and characterize plant immunity-activating microorganisms in Brassicaceae plants.
RESULTS
A total of 25 bacterial strains were isolated from the interior of a Brassicaceae plant, Raphanus sativus var. hortensis. Ten different genera of bacteria were identified: Pseudomonas, Leclercia, Enterobacter, Xanthomonas, Rhizobium, Agrobacterium, Pantoea, Rhodococcus, Microbacterium, and Plantibacter. The isolated strains were analyzed using a method to detect plant immunity-activating microorganisms that involves incubation of the microorganism with tobacco BY-2 cells, followed by treatment with cryptogein, a proteinaceous elicitor of tobacco immune responses. In this method, cryptogein-induced production of reactive oxygen species (ROS) in BY-2 cells serves as a marker of immune activation. Among the 25 strains examined, 6 strains markedly enhanced cryptogein-induced ROS production in BY-2 cells. These 6 strains colonized the interior of Arabidopsis plants, and Pseudomonas sp. RS3R-1 and Rhodococcus sp. RS1R-6 selectively enhanced plant resistance to the bacterial pathogens Pseudomonas syringae pv. tomato DC3000 and Pectobacterium carotovorum subsp. carotovorum NBRC 14082, respectively. In addition, Pseudomonas sp. RS1P-1 effectively enhanced resistance to both pathogens. We also comprehensively investigated the localization (i.e., cellular or extracellular) of the plant immunity-activating components produced by the bacteria derived from R. sativus var. hortensis and the components produced by previously isolated bacteria derived from another Brassicaceae plant species, Brassica rapa var. perviridis. Most gram-negative strains enhanced cryptogein-induced ROS production in BY-2 cells via the presence of cells themselves rather than via extracellular components, whereas many gram-positive strains enhanced ROS production via extracellular components. Comparative genomic analyses supported the hypothesis that the structure of lipopolysaccharides in the outer cell envelope plays an important role in the ROS-enhancing activity of gram-negative Pseudomonas strains.
CONCLUSIONS
The assay method described here based on elicitor-induced ROS production in cultured plant cells enabled the discovery of novel plant immunity-activating bacteria from R. sativus var. hortensis. The results in this study also suggest that components involved in the ROS-enhancing activity of the bacteria may differ depending largely on genus and species.
Topics: Brassicaceae; Reactive Oxygen Species; Arabidopsis; Pseudomonas syringae; Plant Immunity; Plant Diseases
PubMed: 37407947
DOI: 10.1186/s12866-023-02920-y -
International Journal of Clinical... Aug 2023In Europe, Serbia occupies a high position in antibiotic utilization and antimicrobial resistance (AMR).
BACKGROUND
In Europe, Serbia occupies a high position in antibiotic utilization and antimicrobial resistance (AMR).
AIM
The aim was to analyse utilization trends of meropenem, ceftazidime, aminoglycosides, piperacillin/tazobactam and fluoroquinolones (2006-2020), and the reported AMR in Pseudomonas aeruginosa (2013-2020) in Serbia and to compare with data from eight European countries (2015-2020).
METHOD
Joinpoint regression was used to analyse antibiotic utilization data (2006-2020) and the reported AMR in Pseudomonas aeruginosa (2013-2020). Data sources were relevant national and international institutions. Antibiotic utilization and AMR in Pseudomonas aeruginosa data in Serbia were compared with eight European countries.
RESULTS
There was a significantly increased trend for ceftazidime utilization and reported resistance in Pseudomonas aeruginosa, Serbia (p < 0.05) (2018-2020). For ceftazidime, piperacillin/tazobactam, and fluoroquinolones resistances in Pseudomonas aeruginosa an increased trend was observed, Serbia (2013-2020). A decrease in both the utilization of aminoglycosides, Serbia (p < 0.05) (2006-2018) and contemporaneous Pseudomonas aeruginosa resistance (p > 0.05) was detected. Fluoroquinolone utilization (2015-2020) was highest in Serbia compared to Netherlands and Finland, 310 and 305% higher, similar compared to Romania, and 2% less compared to Montenegro. Aminoglycosides (2015-2020) were 2550 and 783% more used in Serbia compared to Finland and Netherlands, and 38% less regarding Montenegro. The highest percentage of Pseudomonas aeruginosa resistance was in Romania and Serbia (2015-2020).
CONCLUSION
The use of piperacillin/tazobactam, ceftazidime and fluoroquinolones should be carefully monitored in clinical practice due to increased Pseudomonas aeruginosa resistance. The level of utilization and AMR in Pseudomonas aeruginosa is still high in Serbia compared to other European countries.
Topics: Humans; Ceftazidime; Pseudomonas aeruginosa; Serbia; Pseudomonas Infections; Anti-Bacterial Agents; Anti-Infective Agents; Aminoglycosides; Fluoroquinolones; Piperacillin, Tazobactam Drug Combination
PubMed: 37284904
DOI: 10.1007/s11096-023-01603-y -
Current Opinion in Infectious Diseases Dec 2023This review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P.... (Review)
Review
PURPOSE OF REVIEW
This review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa , A. baumannii , S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).
RECENT FINDINGS
The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.
SUMMARY
NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.
Topics: Humans; Gram-Negative Bacterial Infections; Gram-Negative Bacteria; Pseudomonas aeruginosa; Virulence Factors
PubMed: 37732777
DOI: 10.1097/QCO.0000000000000969 -
Toxins Aug 2023In this study, a dual-member bacterial consortium with the ability to oxidize deoxynivalenol (DON) to 3-keto-DON, designated SD, was first screened from the feces of...
In this study, a dual-member bacterial consortium with the ability to oxidize deoxynivalenol (DON) to 3-keto-DON, designated SD, was first screened from the feces of larvae. This consortium consisted of sp. SD17-1 and sp. SD17-2, as determined by 16S rRNA-based phylogenetic analysis. A temperature of 30 °C, a pH of 8.0-9.0, and an initial inoculum concentration ratio of to of 0.1 were optimal single-factor parameters for the DON oxidation activity of the bacterial consortium SD. Genome-based bioinformatics analysis revealed the presence of an intact PQQ biosynthesis operon () and four putative pyrroloquinoline quinone (PQQ)-dependent alcohol dehydrogenase (ADH) genes in the genomes of strain SD17-1 and strain SD17-2, respectively. Biochemical analyses further confirmed the PQQ-producing phenotype of and the DON-oxidizing enzymatic activities of two of four PQQ-dependent ADHs in . The addition of PQQ-containing a cell-free fermentation supernatant from activated DON-oxidizing activity of . In summary, as members of the bacterial consortium SD, and play indispensable and complementary roles in SD's oxidation of DON. Specifically, is responsible for producing the necessary PQQ cofactor, whereas expresses the PQQ-dependent DON dehydrogenase, together facilitating the oxidation of DON.
Topics: Animals; Phylogeny; RNA, Ribosomal, 16S; Tenebrio; Biotransformation; Feces; Larva; PQQ Cofactor; Pseudomonas
PubMed: 37624249
DOI: 10.3390/toxins15080492 -
Proceedings of the National Academy of... Oct 2023Energy conversion by electron transport chains occurs through the sequential transfer of electrons between protein complexes and intermediate electron carriers, creating...
Energy conversion by electron transport chains occurs through the sequential transfer of electrons between protein complexes and intermediate electron carriers, creating the proton motive force that enables ATP synthesis and membrane transport. These protein complexes can also form higher order assemblies known as respiratory supercomplexes (SCs). The electron transport chain of the opportunistic pathogen is closely linked with its ability to invade host tissue, tolerate harsh conditions, and resist antibiotics but is poorly characterized. Here, we determine the structure of a SC that forms between the quinol:cytochrome oxidoreductase (cytochrome ) and one of the organism's terminal oxidases, cytochrome , which is found only in some bacteria. Remarkably, the SC structure also includes two intermediate electron carriers: a diheme cytochrome and a single heme cytochrome . Together, these proteins allow electron transfer from ubiquinol in cytochrome to oxygen in cytochrome . We also present evidence that different isoforms of cytochrome can participate in formation of this SC without changing the overall SC architecture. Incorporating these different subunit isoforms into the SC would allow the bacterium to adapt to different environmental conditions. Bioinformatic analysis focusing on structural motifs in the SC suggests that cytochrome - SCs also exist in other bacterial pathogens.
Topics: Pseudomonas aeruginosa; Electron Transport; Biological Transport; Cytochromes c; Anti-Bacterial Agents
PubMed: 37751552
DOI: 10.1073/pnas.2307093120