Recent Advances of Respiratory Infections

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 18207

Special Issue Editors


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Guest Editor
Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Japan
Interests: diagnostic methods for pleural effusion; lung sounds; Mycoplasma pneumoiae; pneumonia; respiratory viruses
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Guest Editor
Department of Pediatrics, Laboratory of Pediatrics, Erasmus MC-Sophia Children’s Hospital, University Medical Centre Rotterdam, Rotterdam, The Netherlands
Interests: host-pathogen interactions; antigen presenting cells; pediatric respiratory infections; Mycoplasmas; M. pneumoniae
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Guest Editor
Department of Pediatrics, Leader of Infection Control Team, Kawasaki Medical School, Kurashiki, Japan
Interests: multidrug-resistant pathogens; antimicrobial therapy; pneumonia
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Special Issue Information

Dear Colleagues,

In this COVID-19 era, diagnostic methods and/or techniques for respiratory infections have been developed. However, these advanced methods, in turn, attract lots of attention for the principles or clinical pitfalls of handling patients with respiratory infections. In this Special Issue of Microorganisms, we invite you to submit contributions concerning any aspects related to respiratory infections including respiratory viruses, bacteria, and fungi. In addition, we also welcome original research, review papers or case reports describing host-pathogen interactions (i.e., translational research), antimicrobial resistance, and virulence factors of pathogens in respiratory tract infections.

Dr. Takeshi Saraya
Dr. Wendy Unger
Dr. Tomohiro Oishi
Guest Editors

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Keywords

  • respiratory viruses
  • fungus
  • bacteria
  • respiratory tract infection
  • Mycoplasma pneumoniae
  • clinical and critical pitfalls

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Published Papers (7 papers)

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Research

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13 pages, 4834 KiB  
Article
In Silico Identification and In Vitro Validation of Repurposed Compounds Targeting the RSV Polymerase
by Eric Xu, Seohyun Park, Juan Calderon, Dongdong Cao and Bo Liang
Microorganisms 2023, 11(6), 1608; https://doi.org/10.3390/microorganisms11061608 - 18 Jun 2023
Cited by 1 | Viewed by 3175
Abstract
Respiratory Syncytial Virus (RSV) is the top cause of infant hospitalization globally, with no effective treatments available. Researchers have sought small molecules to target the RNA-dependent RNA Polymerase (RdRP) of RSV, which is essential for replication and transcription. Based on the cryo-EM structure [...] Read more.
Respiratory Syncytial Virus (RSV) is the top cause of infant hospitalization globally, with no effective treatments available. Researchers have sought small molecules to target the RNA-dependent RNA Polymerase (RdRP) of RSV, which is essential for replication and transcription. Based on the cryo-EM structure of the RSV polymerase, in silico computational analysis including molecular docking and the protein-ligand simulation of a database, including 6554 molecules, is currently undergoing phases 1–4 of clinical trials and has resulted in the top ten repurposed compound candidates against the RSV polymerase, including Micafungin, Totrombopag, and Verubecestat. We performed the same procedure to evaluate 18 small molecules from previous studies and chose the top four compounds for comparison. Among the top identified repurposed compounds, Micafungin, an antifungal medication, showed significant inhibition and binding affinity improvements over current inhibitors such as ALS-8112 and Ribavirin. We also validated Micafungin’s inhibition of the RSV RdRP using an in vitro transcription assay. These findings contribute to RSV drug development and hold promise for broad-spectrum antivirals targeting the non-segmented negative-sense (NNS) RNA viral polymerases, including those of rabies (RABV) and Ebola (EBOV). Full article
(This article belongs to the Special Issue Recent Advances of Respiratory Infections)
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11 pages, 962 KiB  
Communication
Total Osteopontin and Its Isoform OPN4 Are Differently Expressed in Respiratory Samples during Influenza A(H1N1)pdm09 Infection and Progression
by Jéssica Santa Cruz de Carvalho Martins, Thiago das Chagas Sousa, Maria de Lourdes de Aguiar Oliveira, Etel Rodrigues Pereira Gimba, Marilda Mendonça Siqueira and Aline da Rocha Matos
Microorganisms 2023, 11(5), 1349; https://doi.org/10.3390/microorganisms11051349 - 20 May 2023
Viewed by 1562
Abstract
Influenza A virus (IAV) infection affects the human respiratory tract, causing an acute and highly contagious disease. Individuals with comorbidities and in the extremes of age are classified as risk groups for serious clinical outcomes. However, part of the severe infections and fatalities [...] Read more.
Influenza A virus (IAV) infection affects the human respiratory tract, causing an acute and highly contagious disease. Individuals with comorbidities and in the extremes of age are classified as risk groups for serious clinical outcomes. However, part of the severe infections and fatalities are observed among young healthy individuals. Noteworthy, influenza infections lack specific prognostic biomarkers that would predict the disease severity. Osteopontin (OPN) has been proposed as a biomarker in a few human malignancies and its differential modulation has been observed during viral infections. However, OPN expression levels in the primary site of IAV infection have not been previously investigated. Therefore, we evaluated the transcriptional expression patterns of total OPN (tOPN) and its splicing isoforms (OPNa, OPNb, OPNc, OPN4, and OPN5) in 176 respiratory secretion samples collected from human influenza A(H1N1)pdm09 cases and a group of 65 IAV-negative controls. IAV samples were differentially classified according to their disease severity. tOPN was more frequently detected in IAV samples (34.1%) when compared with the negative controls (18.5%) (p < 0.05), as well as in fatal (59.1%) versus non-fatal IAV samples (30.5%) (p < 0.01). OPN4 splice variant transcript was more prevalent in IAV cases (78.4%) than in the negative controls (66.1%) (p = 0.05) and in severe cases (85.7%) in relation to the non-severe ones (69.2%) (p < 0.01). OPN4 detection was also associated with severity symptoms such as dyspnea (p < 0.05), respiratory failure (p < 0.05), and oxygen saturation < 95% (p < 0.05). In addition, the OPN4 expression level was increased in the fatal cases of respiratory samples. Our data indicated that tOPN and OPN4 had a more pronounced expression pattern in IAV respiratory samples, pointing to the potential use of these molecules as biomarkers to evaluate disease outcomes. Full article
(This article belongs to the Special Issue Recent Advances of Respiratory Infections)
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8 pages, 910 KiB  
Communication
Viral and Bacterial Respiratory Pathogens during the COVID-19 Pandemic in Israel
by Yonatan Oster, Wiessam Abu Ahmad, Ayelet Michael-Gayego, Mila Rivkin, Leonid Levinzon, Dana Wolf, Ran Nir-Paz and Hila Elinav
Microorganisms 2023, 11(1), 166; https://doi.org/10.3390/microorganisms11010166 - 9 Jan 2023
Cited by 6 | Viewed by 2570
Abstract
Background: previous worldwide reports indicated a substantial short-term reduction in various respiratory infections during the early phase of the SARS-CoV-2 pandemic. Aims: exploring the long-term impact of the COVID-19 pandemic on respiratory pathogens. Methods: retrospective analysis of bacterial and viral positivity rate in [...] Read more.
Background: previous worldwide reports indicated a substantial short-term reduction in various respiratory infections during the early phase of the SARS-CoV-2 pandemic. Aims: exploring the long-term impact of the COVID-19 pandemic on respiratory pathogens. Methods: retrospective analysis of bacterial and viral positivity rate in respiratory samples, between 1 January 2017–30 June 2022 in a tertiary hospital in Jerusalem, Israel. Results: A decline in overall respiratory tests and positivity rate was observed in the first months of the pandemic. Respiratory isolations of Hemophilus influenza and Streptococcus pneumoniae were insignificantly affected and returned to their monthly average by November 2020, despite a parallel surge in COVID-19 activity, while Mycoplasma pneumoniae was almost eliminated from the respiratory pathogens scene. Each viral pathogen acted differently, with adenovirus affected only for few months. Human-metapneumovirus and respiratory-syncytial-virus had reduced activity for approximately a year, and influenza A virus resurged in November 2021 with the elimination of Influenza-B. Conclusions: After an immediate decline in non-SARS-CoV-2 respiratory infections, each pathogen has a different pattern during a 2-year follow-up. These patterns might be influenced by intrinsic factors of each pathogen and different risk reduction behaviors of the population. Since some of these measures will remain in the following years, we cannot predict the timing of return to pre-COVID-19 normalcy. Full article
(This article belongs to the Special Issue Recent Advances of Respiratory Infections)
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8 pages, 1201 KiB  
Article
Recent Trend of Antimicrobial Susceptibility among Mycoplasma pneumoniae Isolated from Japanese Children
by Tomohiro Oishi, Daisuke Yoshioka, Takashi Nakano and Kazunobu Ouchi
Microorganisms 2022, 10(12), 2428; https://doi.org/10.3390/microorganisms10122428 - 8 Dec 2022
Cited by 3 | Viewed by 3001
Abstract
Macrolide-resistant Mycoplasma pneumoniae (MRMP) infections have become increasingly prevalent, especially in East Asia. Whereas MRMP strains have point mutations that are implicated in conferring resistance, monitoring the antibiotic susceptibility of M. pneumoniae and identifying mutations in the resistant strains is crucial for effective [...] Read more.
Macrolide-resistant Mycoplasma pneumoniae (MRMP) infections have become increasingly prevalent, especially in East Asia. Whereas MRMP strains have point mutations that are implicated in conferring resistance, monitoring the antibiotic susceptibility of M. pneumoniae and identifying mutations in the resistant strains is crucial for effective disease management. Therefore, we investigated antimicrobial susceptibilities among M. pneumoniae isolates obtained from Japanese children since 2011. To establish the current susceptibility trend, we analyzed the minimum inhibitory concentrations (MICs) of M. pneumoniae in recent years (2017–2020) in comparison with past data. Our observation of 122 M. pneumoniae strains suggested that 76 were macrolide-susceptible M. pneumoniae (MSMP) and 46 were macrolide-resistant. The MIC ranges (µg/mL) of clarithromycin (CAM), azithromycin (AZM), tosufloxacin (TFLX), and minocycline (MINO) to all M. pneumoniae isolates were 0.001–>128, 0.00012–>128, 0.25–0.5, and 0.125–4 µg/mL, respectively. None of the strains was resistant to TFLX or MINO. The MIC distributions of CAM and AZM to MSMP and MINO to all M. pneumoniae isolates were significantly lower, but that of TFLX was significantly higher than that reported in all previous data concordant with the amount of recent antimicrobial use. Therefore, continuation of appropriate antimicrobial use for M. pneumoniae infection is important. Full article
(This article belongs to the Special Issue Recent Advances of Respiratory Infections)
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9 pages, 260 KiB  
Article
Trends in Asymptomatic Nasopharyngeal Streptococcus pneumoniae Carriage with qPCR and Culture Analysis
by Julie-Anne Lemay, Leah J. Ricketson and James D. Kellner
Microorganisms 2022, 10(10), 2074; https://doi.org/10.3390/microorganisms10102074 - 20 Oct 2022
Viewed by 1607
Abstract
We previously reported trends in pneumococcal nasopharyngeal carriage in the post-PCV13 era as detected by conventional culture methods. Our current aim is to assess if there are fundamental differences in the clinical and demographic features of children who have pneumococcal carriage detected by [...] Read more.
We previously reported trends in pneumococcal nasopharyngeal carriage in the post-PCV13 era as detected by conventional culture methods. Our current aim is to assess if there are fundamental differences in the clinical and demographic features of children who have pneumococcal carriage detected by qPCR compared with culture analysis. The CASPER team conducted point-prevalence surveys in 2016 in healthy children in Calgary to determine trends in overall and serotype-specific pneumococcal nasopharyngeal carriage. Being 18 months of age (p = 0.009), having at least one sibling under 2 years of age (p = 0.04), having only sibling(s) over 2 years of age (p = 0.001), and childcare attendance (p = 0.005) were associated with carriage by qPCR methods only. Having only sibling(s) older than 2 years of age was associated with carriage detected by both qPCR and culture methods (p = 0.001). No clinical factors were associated with carriage detected by both qPCR and culture compared to qPCR methods only. Both analyses are suitable methods to detect carriage; however, qPCR analysis is more sensitive and more cost-effective. As there are no fundamental differences in the children that have pneumococcal nasopharyngeal carriage detectable by qPCR methods compared to conventional culture methods, molecular analysis may be a preferable option for future carriage studies. Full article
(This article belongs to the Special Issue Recent Advances of Respiratory Infections)
12 pages, 2713 KiB  
Article
Live Influenza Vaccine Provides Early Protection against Homologous and Heterologous Influenza and May Prevent Post-Influenza Pneumococcal Infections in Mice
by Yulia Desheva, Galina Leontieva, Tatiana Kramskaya, Igor Losev, Andrey Rekstin, Nadezhda Petkova, Polina Kudar and Alexander Suvorov
Microorganisms 2022, 10(6), 1150; https://doi.org/10.3390/microorganisms10061150 - 2 Jun 2022
Cited by 2 | Viewed by 1952
Abstract
Influenza and S. pneumoniae infections are a significant cause of morbidity and mortality worldwide. Intranasal live influenza vaccine (LAIV) may prevent influenza-related bacterial complications. The objectives of the study are to estimate resistance against early influenza infection and post-influenza pneumococcal pneumonia after LAIV [...] Read more.
Influenza and S. pneumoniae infections are a significant cause of morbidity and mortality worldwide. Intranasal live influenza vaccine (LAIV) may prevent influenza-related bacterial complications. The objectives of the study are to estimate resistance against early influenza infection and post-influenza pneumococcal pneumonia after LAIV in mice. Mice were administered intranasally the monovalent LAIV A/17/Mallard Netherlands/00/95(H7N3), A/17/South Africa/2013/01(H1N1)pdm09 or trivalent LAIV 2017–2018 years of formulation containing A/17/New York/15/5364(H1N1)pdm09 vaccine strain. LAIV demonstrated early protection against homologous and heterologous infections with A/South Africa/3626/2013 (H1N1) pdm09 influenza virus on day six, following immunization. Following boost immunization, trivalent LAIV demonstrated a pronounced protective effect both in terms of lethality and pneumococcal lung infection when S. pneumoniae infection was performed three days after the onset of influenza infection. Conclusion: LAIV provides early protection against homologous and heterologous viral infections and has a protective effect against post-influenza pneumococcal infection. These data suggest that the intranasal administration of LAIV may be useful during the cycle of circulation not only of influenza viruses, but also of other causative agents of acute respiratory infections. Full article
(This article belongs to the Special Issue Recent Advances of Respiratory Infections)
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Review

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13 pages, 574 KiB  
Review
A Fatal Case of Pseudomonas aeruginosa Community-Acquired Pneumonia in an Immunocompetent Patient: Clinical and Molecular Characterization and Literature Review
by Nicole Barp, Matteo Marcacci, Emanuela Biagioni, Lucia Serio, Stefano Busani, Paolo Ventura, Erica Franceschini, Gabriella Orlando, Claudia Venturelli, Ilaria Menozzi, Martina Tambassi, Erika Scaltriti, Stefano Pongolini, Mario Sarti, Antonello Pietrangelo, Massimo Girardis, Cristina Mussini and Marianna Meschiari
Microorganisms 2023, 11(5), 1112; https://doi.org/10.3390/microorganisms11051112 - 24 Apr 2023
Cited by 3 | Viewed by 3280
Abstract
Rare cases of Pseudomonas aeruginosa community-acquired pneumonia (PA-CAP) were reported in non-immunocompromised patients. We describe a case of Pseudomonas aeruginosa (PA) necrotizing cavitary CAP with a fatal outcome in a 53-year-old man previously infected with SARS-CoV-2, who was admitted for dyspnea, fever, cough, [...] Read more.
Rare cases of Pseudomonas aeruginosa community-acquired pneumonia (PA-CAP) were reported in non-immunocompromised patients. We describe a case of Pseudomonas aeruginosa (PA) necrotizing cavitary CAP with a fatal outcome in a 53-year-old man previously infected with SARS-CoV-2, who was admitted for dyspnea, fever, cough, hemoptysis, acute respiratory failure and a right upper lobe opacification. Six hours after admission, despite effective antibiotic therapy, he experienced multi-organ failure and died. Autopsy confirmed necrotizing pneumonia with alveolar hemorrhage. Blood and bronchoalveolar lavage cultures were positive for PA serotype O:9 belonging to ST1184. The strain shares the same virulence factor profile with reference genome PA01. With the aim to better investigate the clinical and molecular characteristics of PA-CAP, we considered the literature of the last 13 years concerning this topic. The prevalence of hospitalized PA-CAP is about 4% and has a mortality rate of 33–66%. Smoking, alcohol abuse and contaminated fluid exposure were the recognized risk factors; most cases presented the same symptoms described above and needed intensive care. Co-infection of PA-influenza A is described, which is possibly caused by influenza-inducing respiratory epithelial cell dysfunction: the same pathophysiological mechanism could be assumed with SARS-CoV-2 infection. Considering the high rate of fatal outcomes, additional studies are needed to identify sources of infections and new risk factors, along with genetic and immunological features. Current CAP guidelines should be revised in light of these results. Full article
(This article belongs to the Special Issue Recent Advances of Respiratory Infections)
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