Biofilm formation is a key virulence factor for a wide range of microorganisms that cause chronic infections. The multifactorial nature of biofilm development and drug tolerance imposes great challenges for the use of conventional antimicrobials and indicates the need for multi-targeted or combinatorial therapies. In this Review, we focus on current therapeutic strategies and those under development that target vital structural and functional traits of microbial biofilms and drug tolerance mechanisms, including the extracellular matrix and dormant cells. We emphasize strategies that are supported by in vivo or ex vivo studies, highlight emerging biofilm-targeting technologies and provide a rationale for multi-targeted therapies aimed at disrupting the complex biofilm microenvironment.

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Targeting microbial biofilms: current and prospective therapeutic strategies.

To determine distribution of severe acute respiratory syndrome coronavirus 2 in hospital wards in Wuhan, China, we tested air and surface samples. Contamination was greater in intensive care units than general wards. Virus was widely distributed on floors, computer mice, trash cans, and sickbed handrails and was detected in air ≈4 m from patients.

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Aerosol and Surface Distribution of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospital Wards, Wuhan, China, 2020.

For millions of years, our resident microbes have coevolved and coexisted with us in a mostly harmonious symbiotic relationship. We are not distinct entities from our microbiome, but together we form a 'superorganism' or holobiont, with the microbiome playing a significant role in our physiology and health. The mouth houses the second most diverse microbial community in the body, harbouring over 700 species of bacteria that colonise the hard surfaces of teeth and the soft tissues of the oral mucosa. Through recent advances in technology, we have started to unravel the complexities of the oral microbiome and gained new insights into its role during both health and disease. Perturbations of the oral microbiome through modern-day lifestyles can have detrimental consequences for our general and oral health. In dysbiosis, the finely-tuned equilibrium of the oral ecosystem is disrupted, allowing disease-promoting bacteria to manifest and cause conditions such as caries, gingivitis and periodontitis. For practitioners and patients alike, promoting a balanced microbiome is therefore important to effectively maintain or restore oral health. This article aims to give an update on our current knowledge of the oral microbiome in health and disease and to discuss implications for modern-day oral healthcare.

https://research.birmingham.ac.uk/portal/files/33444697/Kilian_et_al_BDJ_2016.pdf

The oral microbiome – an update for oral healthcare professionals

Coronavirus Disease 19 (COVID-19): Implications for Clinical Dental Care.

病毒性肺炎常为吸入性感染,主要传染源是病人,通过飞沫和密切接触传染,可由上呼吸道病毒感染向下蔓延引起,也可继发于出疹性病毒感染,常伴气管-支气管感染.流行性感冒病毒是成年人和老人病毒性肺炎最为常见的病原,婴幼儿病毒性肺炎则常由呼吸道合胞病毒感染所致.其他如副流感病毒、巨细胞病毒、冠状病毒、腺病毒、鼻病毒和某些肠道病毒,如柯萨奇、埃可病毒等也可引起病毒性肺炎.在非细菌性肺炎中,病毒性肺炎占25%～50%,多发生于冬春季节,可散发或流行,多见于婴幼儿、老年人和原有慢性心肺疾病的病人.近年来由于免疫抑制药物广泛应用于器官移植病人,以及爱滋病发病人数的增多,病毒性肺炎的发病率逐渐增多,而SARS的流行使得病毒性肺炎显得尤为重要.一般的病毒性肺炎临床表现大多轻微,与支原体肺炎症状相似,病程1～2周.但重症肺炎可有持续高热、心悸、气急、呼吸困难、发绀,还可伴有休克和呼吸衰竭。

Viral pneumonia

A novel β-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal–oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.

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Transmission routes of 2019-nCoV and controls in dental practice.

Microbes colonize human oral surfaces within hours after delivery. During postnatal development, physiological changes, such as the eruption of primary teeth and replacement of the primary dentition with permanent dentition, greatly alter the microbial habitats, which, in return, may lead to community composition shifts at different phases in people's lives. By profiling saliva, supragingival and mucosal plaque samples from healthy volunteers at different ages and dentition stages, we observed that the oral cavity is a highly heterogeneous ecological system containing distinct niches with significantly different microbial communities. More importantly, the phylogenetic microbial structure varies with ageing. In addition, only a few taxa were present across the whole populations, indicating a core oral microbiome should be defined based on age and oral niches.

Oral cavity contains distinct niches with dynamic microbial communities.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel β-coronavirus, is the main pathogenic agent of the rapidly spreading pneumonia called coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects much more people, especially the elder population, around the world than other coronavirus, such as SARS-CoV and MERS-CoV, which is challenging current global public health system. Beyond the pathogenesis of SARS-CoV-2, microbial coinfection plays an important role in the occurrence and development of SARS-CoV-2 infection by raising the difficulties of diagnosis, treatment, prognosis of COVID-19, and even increasing the disease symptom and mortality. We summarize the coinfection of virus, bacteria and fungi with SARS-CoV-2, their effects on COVID-19, the reasons of coinfection, and the diagnosis to emphasize the importance of microbial coinfection in COVID-19. • Microbial coinfection is a nonnegligible factor in COVID-19. • Microbial coinfection exacerbates the processes of the occurrence, development and prognosis of COVID-19, and the difficulties of clinical diagnosis and treatment. • Different virus, bacteria, and fungi contributed to the coinfection with SARS-CoV-2.

/pdf/the-microbial-coinfection-in-covid-19-449w97b7bu.pdf

The microbial coinfection in COVID-19.

SARS-CoV-2, a novel emerging coronavirus, has caused severe disease (COVID-19), and rapidly spread worldwide since the beginning of 2020. SARS-CoV-2 mainly spreads by coughing, sneezing, droplet inhalation, and contact. SARS-CoV-2 has been detected in saliva samples, making saliva a potential transmission route for COVID-19. The participants in dental practice confront a particular risk of SARS-CoV-2 infection due to close contact with the patients and potential exposure to saliva-contaminated droplets and aerosols generated during dental procedures. In addition, saliva-contaminated surfaces could lead to potential cross-infection. Hence, the control of saliva-related transmission in the dental clinic is critical, particularly in the epidemic period of COVID-19. Based on our experience of the COVID-19 epidemic, some protective measures that can help reduce the risk of saliva-related transmission are suggested, in order to avoid the potential spread of SARS-CoV-2 among patients, visitors, and dental practitioners.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/omi.12289

Saliva is a non-negligible factor in the spread of COVID-19.

Dental plaque biofilms are responsible for numerous chronic oral infections and cause a severe health burden. Many of these infections cannot be eliminated, as the bacteria in the biofilms are resistant to the host's immune defenses and antibiotics. There is a critical need to develop new strategies to control biofilm-based infections. Biofilm formation in Streptococcus mutans is promoted by major virulence factors known as glucosyltransferases (Gtfs), which synthesize adhesive extracellular polysaccharides (EPS). The current study was designed to identify novel molecules that target Gtfs, thereby inhibiting S. mutans biofilm formation and having the potential to prevent dental caries. Structure-based virtual screening of approximately 150,000 commercially available compounds against the crystal structure of the glucosyltransferase domain of the GtfC protein from S. mutans resulted in the identification of a quinoxaline derivative, 2-(4-methoxyphenyl)-N-(3-{[2-(4-methoxyphenyl)ethyl]imino}-1,4-dihydro-2-quinoxalinylidene)ethanamine, as a potential Gtf inhibitor. In vitro assays showed that the compound was capable of inhibiting EPS synthesis and biofilm formation in S. mutans by selectively antagonizing Gtfs instead of by killing the bacteria directly. Moreover, the in vivo anti-caries efficacy of the compound was evaluated in a rat model. We found that the compound significantly reduced the incidence and severity of smooth and sulcal-surface caries in vivo with a concomitant reduction in the percentage of S. mutans in the animals' dental plaque (P < 0.05). Taken together, these results represent the first description of a compound that targets Gtfs and that has the capacity to inhibit biofilm formation and the cariogenicity of S. mutans.

Yuqing Li

Papers

Transmission routes of 2019-nCoV and controls in dental practice.

Oral cavity contains distinct niches with dynamic microbial communities.

The microbial coinfection in COVID-19.

Saliva is a non-negligible factor in the spread of COVID-19.

Molecule Targeting Glucosyltransferase Inhibits Streptococcus mutans Biofilm Formation and Virulence