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Host-Pathogen Interactions during Persistent Bacterial Infections
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Host-Pathogen Interactions during Persistent Bacterial Infections

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (25 December 2023) | Viewed by 9534

Special Issue Editors

Dr. Lorena Tuchscherr

E-Mail Website
Guest Editor
Institute of Medical Microbiology, Jena University Hospital, 07747 Jena, Germany
Interests: host-pathogen interaction; bacterial interaction; chronic infections; dormant bacterial phenotype
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Bettina Löffler

E-Mail Website
Guest Editor
Institute of Medical Microbiology, Jena University Hospital, Am Klinikum 1, D-07747 Jena, Germany
Interests: toxin-mediated effects in bacterial infections and viral-bacterial co-infections; persistence strategies of pathogens; infection models and testing of therapy strategies; diagnostic microbiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

One of the main bacterial strategies during persistence is to manipulate the host response to promote microbial survival. Bacterial adaptation is frequently used by pathogens upon the transition from the free-living state to an intracellular environment. In this scenario, bacterial pathogens regulate their virulence factors, phenotype and metabolic pathways to persist silently for long periods of time. The microbes are able to establish a niche to avoid their eradication despite antimicrobials and immune response. However, the persisting pathogens can escape from their niche, regain full virulence and develop a new episode of an infection. Thus, the study of bacterial adaptation to the host plays an important role in the progress of disease from acute to chronic and relapse infections. 

On the other hand, the host competes with bacteria for nutrients and survival. Thus, host cells adapt their metabolic pathways to activate the bacterial clearance. This type of interaction between host and pathogen determines the outcome of the infection.

This Special Issue is dedicated to understanding the mechanisms that take place during the bacterial switch from an aggressive virulent to a silent persisting phenotype. Furthermore, changes induced by pathogens on host cells that promote bacterial persistence should be taken into consideration. Reviews and research articles focusing on understanding the interchange between the different phenotypes by multiple approaches that include molecular and cell biology tools, advanced imaging tools and -omics techniques are welcome.

Dr. Lorena Tuchscherr
Prof. Dr. Bettina Löffler
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bacteria
  • intracellular adaptation
  • metabolic adaptation
  • metabolic host reprogramming
  • host–pathogen interaction
  • chronic infections
  • regulation of virulence

Published Papers (6 papers)

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Research

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20 pages, 7449 KiB  
Article
Reduced Glycolysis and Cytotoxicity in Staphylococcus aureus Isolates from Chronic Rhinosinusitis as Strategies for Host Adaptation
by Lorena Tuchscherr, Sindy Wendler, Rakesh Santhanam, Juliane Priese, Annett Reissig, Elke Müller, Rida Ali, Sylvia Müller, Bettina Löffler, Stefan Monecke, Ralf Ehricht and Orlando Guntinas-Lichius
Int. J. Mol. Sci. 2024, 25(4), 2229; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25042229 - 13 Feb 2024
Viewed by 949
Abstract
Chronic rhinosinusitis (CRS) is a multifactorial infection of the nasal cavity and sinuses. In this study, nasal swabs from control donors (N = 128) and patients with CRS (N = 246) were analysed. Culture methods and metagenomics revealed no obvious differences in the [...] Read more.
Chronic rhinosinusitis (CRS) is a multifactorial infection of the nasal cavity and sinuses. In this study, nasal swabs from control donors (N = 128) and patients with CRS (N = 246) were analysed. Culture methods and metagenomics revealed no obvious differences in the composition of the bacterial communities between the two groups. However, at the functional level, several metabolic pathways were significantly enriched in the CRS group compared to the control group. Pathways such as carbohydrate transport metabolism, ATP synthesis, cofactors and vitamins, photosynthesis and transcription were highly enriched in CRS. In contrast, pathways related to lipid metabolism were more representative in the control microbiome. As S. aureus is one of the main species found in the nasal cavity, staphylococcal isolates from control and CRS samples were analysed by microarray and functional assays. Although no significant genetic differences were detected by microarray, S. aureus from CRS induced less cytotoxicity to lung cells and lower rates of glycolysis in host cells than control isolates. These results suggest the differential modulation of staphylococcal virulence by the environment created by other microorganisms and their interactions with host cells in control and CRS samples. These changes were reflected in the differential expression of cytokines and in the expression of Agr, the most important quorum-sensing regulator of virulence in S. aureus. In addition, the CRS isolates remained stable in their cytotoxicity, whereas the cytotoxic activity of S. aureus isolated from control subjects decreased over time during in vitro passage. These results suggest that host factors influence the virulence of S. aureus and promote its adaptation to the nasal environment during CRS. Full article
(This article belongs to the Special Issue Host-Pathogen Interactions during Persistent Bacterial Infections)
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19 pages, 2983 KiB  
Article
Extensive Expression of the Virulome Related to Antibiotic Genotyping in Nosocomial Strains of Klebsiella pneumoniae
by Gloria Luz Paniagua-Contreras, Areli Bautista-Cerón, Rosario Morales-Espinosa, Gabriela Delgado, Felipe Vaca-Paniagua, Clara Estela Díaz-Velásquez, Aldo Hugo de la Cruz-Montoya, Luis Rey García-Cortés, María Patricia Sánchez-Yáñez and Eric Monroy-Pérez
Int. J. Mol. Sci. 2023, 24(19), 14754; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241914754 - 29 Sep 2023
Viewed by 908
Abstract
The emergence of hyper-virulent and multidrug-resistant (MDR) strains of Klebsiella pneumoniae isolated from patients with hospital- and community-acquired infections is a serious health problem that increases mortality. The molecular analysis of virulome expression related to antimicrobial-resistant genotype and infection type in K. pneumoniae [...] Read more.
The emergence of hyper-virulent and multidrug-resistant (MDR) strains of Klebsiella pneumoniae isolated from patients with hospital- and community-acquired infections is a serious health problem that increases mortality. The molecular analysis of virulome expression related to antimicrobial-resistant genotype and infection type in K. pneumoniae strains isolated from patients with hospital- and community-acquired infections has been poorly studied. In this study, we analyzed the overall expression of the virulence genotype associated with the antimicrobial resistance genotype and pulse field gel electrophoresis (PFGE) type (PFtype) in K. pneumoniae. We studied 25 strains of K. pneumoniae isolated from patients who developed bacteremia and pneumonia during their hospital stay and 125 strains from outpatients who acquired community-acquired infections. Susceptibility to 12 antimicrobials was determined by Kirby–Bauer. The identification of K. pneumoniae and antibiotic-resistance genes was performed using polymerase chain reaction (PCR). To promote the expression of the virulence genes of K. pneumoniae, an in vitro infection model was used in human epithelial cell lines A549 and A431. Bacterial RNA was extracted with the QIAcube robotic workstation, and reverse transcription to cDNA was performed with the Reverse Transcription QuantiTect kit (Qiagen). The determination of the expression of the virulence genes was performed by real-time PCR. In addition, 57.3% (n = 86) of the strains isolated from patients with hospital- and community-acquired infections were multidrug-resistant (MDR), mainly to beta-lactam antibiotics (CB, AM, CFX, and CF), aminoglycosides (GE), quinolones (CPF and NOF), nitrofurantoin (NF), and sulfamethoxazole/trimethoprim (SXT). The most frequently expressed genes among strains isolated from hospital- and community-acquired infections were adhesion-type, ycfm (80%), mrkD (51.3%), and fimH (30.7%); iron uptake, irp2 (84%), fyuA (68.7%), entB (64.7%), and irp1 (56.7%); and protectins, rpmA (26%), which were related to antibiotic-resistance genes, blaTEM (96%), blaSHV (64%), blaCITM (52.6%), blaCTXM-1 (44.7%), tetA (74%), sul1 (57.3%), aac(3)-IV (40.7%), and aadA1 (36%). The results showed the existence of different patterns of expression of virulome related to the genotype of resistance to antimicrobials and to the PFtypes in the strains of K. pneumoniae that cause hospital- and community-acquired infections. These findings are important and may contribute to improving medical treatment strategies against infections caused by K. pneumoniae. Full article
(This article belongs to the Special Issue Host-Pathogen Interactions during Persistent Bacterial Infections)
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Review

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19 pages, 3496 KiB  
Review
The Recruitment and Activation of Plasminogen by Bacteria—The Involvement in Chronic Infection Development
by Dorota Satala, Aneta Bednarek, Andrzej Kozik, Maria Rapala-Kozik and Justyna Karkowska-Kuleta
Int. J. Mol. Sci. 2023, 24(13), 10436; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241310436 - 21 Jun 2023
Cited by 2 | Viewed by 1124
Abstract
The development of infections caused by pathogenic bacteria is largely related to the specific properties of the bacterial cell surface and extracellular hydrolytic activity. Furthermore, a significant role of hijacking of host proteolytic cascades by pathogens during invasion should not be disregarded during [...] Read more.
The development of infections caused by pathogenic bacteria is largely related to the specific properties of the bacterial cell surface and extracellular hydrolytic activity. Furthermore, a significant role of hijacking of host proteolytic cascades by pathogens during invasion should not be disregarded during consideration of the mechanisms of bacterial virulence. This is the key factor for the pathogen evasion of the host immune response, tissue damage, and pathogen invasiveness at secondary infection sites after initial penetration through tissue barriers. In this review, the mechanisms of bacterial impact on host plasminogen—the precursor of the important plasma serine proteinase, plasmin—are characterized, principally focusing on cell surface exposition of various proteins, responsible for binding of this host (pro)enzyme and its activators or inhibitors, as well as the fibrinolytic system activation tactics exploited by different bacterial species, not only pathogenic, but also selected harmless residents of the human microbiome. Additionally, the involvement of bacterial factors that modulate the process of plasminogen activation and fibrinolysis during periodontitis is also described, providing a remarkable example of a dual use of this host system in the development of chronic diseases. Full article
(This article belongs to the Special Issue Host-Pathogen Interactions during Persistent Bacterial Infections)
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17 pages, 1143 KiB  
Review
How Staphylococcus aureus and Pseudomonas aeruginosa Hijack the Host Immune Response in the Context of Cystic Fibrosis
by Aubin Souche, François Vandenesch, Anne Doléans-Jordheim and Karen Moreau
Int. J. Mol. Sci. 2023, 24(7), 6609; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24076609 - 01 Apr 2023
Cited by 2 | Viewed by 1974
Abstract
Cystic fibrosis (CF) is a serious genetic disease that leads to premature death, mainly due to impaired lung function. CF lungs are characterized by ongoing inflammation, impaired immune response, and chronic bacterial colonization. Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) are the two [...] Read more.
Cystic fibrosis (CF) is a serious genetic disease that leads to premature death, mainly due to impaired lung function. CF lungs are characterized by ongoing inflammation, impaired immune response, and chronic bacterial colonization. Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) are the two most predominant bacterial agents of these chronic infections. Both can colonize the lungs for years by developing host adaptation strategies. In this review, we examined the mechanisms by which SA and PA adapt to the host immune response. They are able to bypass the physical integrity of airway epithelia, evade recognition, and then modulate host immune cell proliferation. They also modulate the immune response by regulating cytokine production and by counteracting the activity of neutrophils and other immune cells. Inhibition of the immune response benefits not only the species that implements them but also other species present, and we therefore discuss how these mechanisms can promote the establishment of coinfections in CF lungs. Full article
(This article belongs to the Special Issue Host-Pathogen Interactions during Persistent Bacterial Infections)
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14 pages, 881 KiB  
Review
Beyond the Clinic: The Activation of Diverse Cellular and Humoral Factors Shapes the Immunological Status of Patients with Active Tuberculosis
by Nancy Liliana Tateosian, María Paula Morelli, Joaquín Miguel Pellegrini and Verónica Edith García
Int. J. Mol. Sci. 2023, 24(5), 5033; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24055033 - 06 Mar 2023
Viewed by 1665
Abstract
Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), has killed nearly one billion people in the last two centuries. Nowadays, TB remains a major global health problem, ranking among the thirteen leading causes of death worldwide. Human TB infection spans [...] Read more.
Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), has killed nearly one billion people in the last two centuries. Nowadays, TB remains a major global health problem, ranking among the thirteen leading causes of death worldwide. Human TB infection spans different levels of stages: incipient, subclinical, latent and active TB, all of them with varying symptoms, microbiological characteristics, immune responses and pathologies profiles. After infection, Mtb interacts with diverse cells of both innate and adaptive immune compartments, playing a crucial role in the modulation and development of the pathology. Underlying TB clinical manifestations, individual immunological profiles can be identified in patients with active TB according to the strength of their immune responses to Mtb infection, defining diverse endotypes. Those different endotypes are regulated by a complex interaction of the patient’s cellular metabolism, genetic background, epigenetics, and gene transcriptional regulation. Here, we review immunological categorizations of TB patients based on the activation of different cellular populations (both myeloid and lymphocytic subsets) and humoral mediators (such as cytokines and lipid mediators). The analysis of the participating factors that operate during active Mtb infection shaping the immunological status or immune endotypes of TB patients could contribute to the development of Host Directed Therapy. Full article
(This article belongs to the Special Issue Host-Pathogen Interactions during Persistent Bacterial Infections)
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24 pages, 473 KiB  
Review
Revisiting Host-Pathogen Interactions in Cystic Fibrosis Lungs in the Era of CFTR Modulators
by Carla M. P. Ribeiro, Matthew G. Higgs, Marianne S. Muhlebach, Matthew C. Wolfgang, Monica Borgatti, Ilaria Lampronti and Giulio Cabrini
Int. J. Mol. Sci. 2023, 24(5), 5010; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24055010 - 05 Mar 2023
Cited by 7 | Viewed by 2138
Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, a new series of therapeutics that correct and potentiate some classes of mutations of the CFTR, have provided a great therapeutic advantage to people with cystic fibrosis (pwCF). The main hindrances of the present CFTR modulators [...] Read more.
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, a new series of therapeutics that correct and potentiate some classes of mutations of the CFTR, have provided a great therapeutic advantage to people with cystic fibrosis (pwCF). The main hindrances of the present CFTR modulators are related to their limitations in reducing chronic lung bacterial infection and inflammation, the main causes of pulmonary tissue damage and progressive respiratory insufficiency, particularly in adults with CF. Here, the most debated issues of the pulmonary bacterial infection and inflammatory processes in pwCF are revisited. Special attention is given to the mechanisms favoring the bacterial infection of pwCF, the progressive adaptation of Pseudomonas aeruginosa and its interplay with Staphylococcus aureus, the cross-talk among bacteria, the bronchial epithelial cells and the phagocytes of the host immune defenses. The most recent findings of the effect of CFTR modulators on bacterial infection and the inflammatory process are also presented to provide critical hints towards the identification of relevant therapeutic targets to overcome the respiratory pathology of pwCF. Full article
(This article belongs to the Special Issue Host-Pathogen Interactions during Persistent Bacterial Infections)
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