Background: Mycoplasma pneumoniae respiratory infections are transmitted by aerosol and droplets in close contact. Aim: We investigated global M. pneumoniae incidence after implementation of non-pharmaceutical interventions (NPIs) against COVID-19 in March 2020. Methods: We surveyed M. pneumoniae detections from laboratories and surveillance systems (national or regional) across the world from 1 April 2020 to 31 March 2021 and compared them with cases from corresponding months between 2017 and 2020. Macrolide-resistant M. pneumoniae (MRMp) data were collected from 1 April 2017 to 31 March 2021. Results: Thirty-seven sites from 21 countries in Europe, Asia, America and Oceania submitted valid datasets (631,104 tests). Among the 30,617 M. pneumoniae detections, 62.39% were based on direct test methods (predominantly PCR), 34.24% on a combination of PCR and serology (no distinction between methods) and 3.37% on serology alone (only IgM considered). In all countries, M. pneumoniae incidence by direct test methods declined significantly after implementation of NPIs with a mean of 1.69% (SD ± 3.30) compared with 8.61% (SD ± 10.62) in previous years (p < 0.01). Detection rates decreased with direct but not with indirect test methods (serology) (–93.51% vs + 18.08%; p < 0.01). Direct detections remained low worldwide throughout April 2020 to March 2021 despite widely differing lockdown or school closure periods. Seven sites (Europe, Asia and America) reported MRMp detections in one of 22 investigated cases in April 2020 to March 2021 and 176 of 762 (23.10%) in previous years (p = 0.04). Conclusions: This comprehensive collection of M. pneumoniae detections worldwide shows correlation between COVID-19 NPIs and significantly reduced detection numbers.

Mycoplasma pneumoniae is one of the most common causes of community-acquired infections of the human upper and lower respiratory tract and can lead to severe and long-lasting interstitial pneumonia [ 1 x 1 Atkinson, TP, Balish, MF, and Waites, KB. Epidemiology, clinical manifestations, pathogenesis and laboratory detection ofMycoplasma pneumoniae infections. FEMS Microbiol Rev. 2008; 32: 956–973 Crossref | PubMed | Scopus (214) | Google Scholar See all References 1 ]. Owing to the fact that mycoplasmas are cell wall-less bacteria, macrolides are in most cases the first choice for antibiotic treatment of M. pneumoniae infections [ 1 x 1 Atkinson, TP, Balish, MF, and Waites, KB. Epidemiology, clinical manifestations, pathogenesis and laboratory detection ofMycoplasma pneumoniae infections. FEMS Microbiol Rev. 2008; 32: 956–973 Crossref | PubMed | Scopus (214) | Google Scholar See all References 1 ]. For young children especially, the alternatives, tetracyclines and new fluoroquinolones, are not recommended. Resistance of isolated strains to macrolides is based on point mutations in domain V of the 23S rRNA gene of M. pneumoniae. An A to G/C transition at position 2063 or 2064 of the gene (M. pneumoniae numbering) resulted in a high-level macrolide resistance of the M. pneumoniae strain, whereas a C to G or C to A mutation at position 2617 was associated with a lower resistance to macrolide antibiotics [ 2 x 2 Bebear, CM and Pereyre, S. Mechanisms of drug resistance inMycoplasma pneumoniae. Curr Drug Targets Infect Disord. 2005; 5: 263–271 Crossref | PubMed | Scopus (36) | Google Scholar See all References , 3 x 3 Pereyre, S, Guyot, C, Renaudin, H, Charron, A, Bebear, C, and Bebear, CM. In vitro selection and characterization of resistance to macrolides and related antibiotics inMycoplasma pneumoniae. Antimicrob Agents Chemother. 2004; 48: 460–465 Crossref | PubMed | Scopus (84) | Google Scholar See all References ].

The obligate pathogenic mycoplasma species Mycoplasma pneumoniae uses a limited but effective repertoire of virulence factors to infect and colonize the human respiratory tract. Besides the development of a unique adhesion complex and the expression of tissue-damaging factors, surface-located glycolytic enzymes and their capacity to bind to components of the human extracellular matrix (ECM) support pathogen–host interactions. Here, we demonstrated that the glycolytic enzymes enolase (Mpn606) and pyruvate dehydrogenase subunit B (Mpn392; PDHB) of M. pneumoniae show concentration-dependent binding to human plasminogen. Monospecific polyclonal antisera against both recombinant proteins reduced the binding to plasminogen significantly. The surface location of PDHB but not of enolase was demonstrated using Triton X fractionation of M. pneumoniae total protein content, membrane fractionation, colony blotting, mild proteolysis of mycoplasma cells, and immunofluorescence tests. To characterize the binding site of plasminogen in surface-displaced PDHB, the mycoplasmal protein was separated into four recombinant proteins followed by investigation of the binding behaviour of peptides that overlap the protein part interacting with plasminogen. Spot analysis resulted in a novel region of 12 amino acids (FPAMFQIFTHAA, position 91 to 102 of PDHB), which is responsible exclusively for binding of human plasminogen and also interacts in a dose-dependent manner with this host protein. The data indicate that the plasminogen-binding enzymes enolase and especially the surface-associated PDHB may contribute to the pathogenesis of M. pneumoniae infections.

Dependent on the excretion pattern, wastewater monitoring of viruses can be a valuable approach to characterizing their circulation in the human population. Using polyethylene glycol precipitation and reverse transcription-quantitative PCR, the occurrence of RNA of SARS-CoV-2 and influenza viruses A/B in the raw wastewater of two treatment plants in Germany between January and May 2022 was investigated. Due to the relatively high incidence in both exposal areas (plant 1 and plant 2), SARS-CoV-2-specific RNA was determined in all 273 composite samples analyzed (concentration of E gene: 1.3 × 10⁴ to 3.2 × 10⁶ gc/L). Despite a nation-wide low number of confirmed infections, influenza virus A was demonstrated in 5.2% (concentration: 9.8 × 10² to 8.4 × 10⁴ gc/L; plant 1) and in 41.6% (3.6 × 10³ to 3.0 × 10⁵ gc/L; plant 2) of samples. Influenza virus B was detected in 36.0% (7.2 × 10² to 8.5 × 10⁶ gc/L; plant 1) and 57.7% (9.6 × 10³ to 2.1 × 10⁷ gc/L; plant 2) of wastewater samples. The results of the study demonstrate the frequent detection of two primary respiratory viruses in wastewater and offer the possibility to track the epidemiology of influenza by wastewater-based monitoring.