ARS-CoV-2 is the causal agent for COVID-19, and the World Health Organization classifies this virus as an airborne pathogen transmitted by asymptomatic, pre-symptomatic and symptomatic individuals through close contact via exposure to infected droplets and aerosols 1,2 . Although SARS-CoV-2 transmission can occur by activities involving the oral cavity, such as speaking, breathing, coughing, sneezing and even singing [3][4][5] , most attention has focused on the nasal-lung axis of infection 6 . Oral manifestations, such as taste loss, dry mouth and oral lesions, are evident in about half of COVID-19 cases [7][8][9] , although it remains unknown whether SARS-CoV-2 can directly infect and replicate in oral tissues, such as the salivary glands (SGs) or mucosa. This is critical because, if these are sites of early infection, they could play an important role in transmitting the virus to the lungs or the gastrointestinal tract via saliva, as has been suggested for other microbial-associated diseases, such as pneumonia 10 and inflammatory bowel diseases 11,12 (Extended Data Fig. 1a).SARS-CoV-2 uses host entry factors, such as ACE2 and TMPRSS family members (TMPRSS2 and TMPRSS4) 13,14 , and understanding the cell types that harbor these receptors is important for determining infection susceptibilities throughout the body [15][16][17] . ACE2 and TMPRSS2 expression has been reported in oral tissues 18,19 ; however, there are no comprehensive descriptions of viral entry factor expression nor direct confirmation of SARS-CoV-2 infection in oral tissues. We hypothesized that SGs and barrier epithelia of the oral cavity and oropharynx can be infected by SARS-CoV-2 and contribute to the transmission of SARS-CoV-2. To test this, we generated two human oral single-cell RNA sequencing (scRNA-seq) atlases to predict cell-specific susceptibilities to SARS-CoV-2 infection. We confirmed ACE2 and TMPRSS expression in SGs and oral mucosa epithelia. SARS-CoV-2 infection was confirmed using autopsy and outpatient samples. Saliva from asymptomatic individuals with COVID-19 demonstrated the potential for viral transmission. In a prospective clinical cohort, we found a positive correlation between salivary viral load and taste loss; we also demonstrated persistent salivary antibody responses to SARS-CoV-2 nucleocapsid and spike proteins. ResultsOral tissue atlases reveal resident immune cells and niche-specific epithelial diversity. The SGs and the barrier mucosa of the oral cavity and oropharynx are likely gateways for viral infection, replication SARS-CoV-2 infection of the oral cavity and saliva

Type III secretion systems (TTSSs) are utilized by numerous bacterial pathogens to inject effector proteins directly into host cells. Using a whole-genome microarray, we investigated the conditions and regulatory factors that control the expression of the Pseudomonas aeruginosa TTSS. The transcriptional response of known TTSS genes indicates a hierarchical pattern of expression in which a set of secretion apparatus and regulatory genes is constitutively expressed. Further analysis of genes coordinately regulated with those encoding the TTSS led to the identification of a signaling pathway that originates from a membrane-associated adenylate cyclase and controls TTSS gene expression. Transcriptome analysis of mutants lacking the ability to synthesize cAMP or the cAMP binding protein Vfr implicated this pathway in the global regulation of host-directed virulence determinants, including the TTSS.

SummaryThe single polar flagellum of Pseudomonas aeruginosa is an important virulence and colonization factor of this opportunistic pathogen. In this study, the annotation of the genes belonging to the fla regulon was updated and their organization was analysed in strains PAK and PAO1, representative type-a and type-b strains of P. aeruginosa respectively. The flagellar genes are clustered in three non-contiguous regions of the chromosome.

A range of anaerobic species are present in large numbers in the lungs of patients with CF. If these anaerobic bacteria are contributing significantly to infection and inflammation in the CF lung, informed alterations to antibiotic treatment to target anaerobes, in addition to the primary infecting pathogens, may improve management.