The threat of antibiotic resistance has attracted strong interest during the last two decades, thus stimulating stewardship programs and research on alternative antimicrobial therapies. Conversely, much less attention has been given to the directly related problem of resistance toward antiseptics and biocides. While bacterial resistances toward triclosan or quaternary ammonium compounds have been considered in this context, the bis-biguanide chlorhexidine (CHX) has been put into focus only very recently when its use was associated with emergence of stable resistance to the last-resort antibiotic colistin. The antimicrobial effect of CHX is based on damaging the bacterial cytoplasmic membrane and subsequent leakage of cytoplasmic material. Consequently, mechanisms conferring resistance toward CHX include multidrug efflux pumps and cell membrane changes. For instance, in staphylococci it has been shown that plasmid-borne qac (“quaternary ammonium compound”) genes encode Qac efflux proteins that recognize cationic antiseptics as substrates. In Pseudomonas stutzeri , changes in the outer membrane protein and lipopolysaccharide profiles have been implicated in CHX resistance. However, little is known about the risk of resistance toward CHX in oral bacteria and potential mechanisms conferring this resistance or even cross-resistances toward antibiotics. Interestingly, there is also little awareness about the risk of CHX resistance in the dental community even though CHX has been widely used in dental practice as the gold-standard antiseptic for more than 40 years and is also included in a wide range of oral care consumer products. This review provides an overview of general resistance mechanisms toward CHX and the evidence for CHX resistance in oral bacteria. Furthermore, this work aims to raise awareness among the dental community about the risk of resistance toward CHX and accompanying cross-resistance to antibiotics. We propose new research directions related to the effects of CHX on bacteria in oral biofilms.

Infection control is critical for the safe delivery of dental care. Infection control practices must be responsive to emerging and re-emerging infectious diseases and outbreaks, as was clearly seen during the peak of the COVID-19 pandemic. An emerging global outbreak of the monkeypox virus has again raised potential challenges for infection control in dentistry. Monkeypox is an infectious disease, characterised by a rash affecting the skin and soft tissues, including the oral cavity. Previously, cases were mostly seen following contact with infected animals in Central and West Africa, with limited human-to-human transmission within and outside of these areas. However, since May 2022, sustained human-to-human transmission has occurred globally. Monkeypox can be transmitted via close contact with an infected person, contaminated objects and surfaces, or by droplets and possibly aerosols, which is therefore of potential importance to dental settings. This article discusses the relevance of monkeypox to dental professionals, the typical presentation of the disease, its potential impact on infection prevention and control practices and the delivery of dental services. The current monkeypox outbreak highlights the need for a more sustained programme of research into dental infection control that can provide a solid evidence base to underpin preparedness planning for future outbreaks and pandemics.

The ability of microorganisms to regulate gene expression is thought to be critical for survival and growth during the development of polymicrobial biofilms such as dental plaque. The commensal dental plaque colonizer, Streptococcus gordonii, responds to cell--cell contact (coaggregation) with Actinomyces oris by regulating >20 genes, including those involved in arginine biosynthesis. We hypothesized that an S. gordonii extracellular protease is critical for sensing by providing amino acids that modulate gene expression. S. gordonii coaggregated strongly with A. oris in buffer, saliva or chemically defined medium (CDM). In wild-type S. gordonii, expression of arginine biosynthesis genes argC and argG increased within two hours' growth in CDM in monocultures, but not following coaggregation with A. oris. By contrast, coaggregation of A. oris with an S. gordonii mutant lacking sgc, encoding the extracellular protease Challisin, resulted in increases in argC and argG gene expression that were similar to monocultures. Genetic complementation of sgc restored the ability of S. gordonii to sense coaggregation with A. oris. Coaggregation enabled growth of S. gordonii in low/no arginine and disruption of sgc did not affect this ability. We propose that extracellular bacterial proteases may be key mediators of cell--cell contact sensing by diverse microbial species.

Background This systematic scoping review aimed to identify changes in biomarkers of microbiological, immunological and biochemical origin during experimental gingivitis (EG) studies that might indicate resistance and resilience. Methods The term ‘experimental gingivitis’ was run in PubMed from inception to April 11th, 2018. From the 411 studies retrieved, 22 studies were included for this review. Results Studies reporting data on biomarker changes during and after full mouth EG trial were included. Two studies reported findings on changes in biomarkers of microbiological, 12 on immunological and eight on biochemical origin. Changes were reported in the induction phase, and occasionally in the resolution phase. The microbiological composition of both supragingival and subgingival dental plaque changed over the course of EG to a more pathogenic direction, but showed a shift back to a more normal composition. This indicates resilience of the oral microbiome. For immunological biomarkers, it was challenging to retrieve a robust pattern of changes across multiple studies. IL-1β and IL-6 in saliva and in gingival crevicular fluid increased during induction phase and returned in the resolution phase below baseline values. The biochemical parameters cystatin-SN, cystatin-S and lactoferrin in saliva were increased at the end of induction phase, however also here no clear pattern emerged based on all available studies. Conclusions More research is needed to investigate which microbiological, immunological, and biochemical biomarkers can be useful for future investigations into the resistance and resilience of the oral cavity to experimental gingivitis.

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The family of human salivary histidine-rich peptides known as histatins bind zinc (Zn) and copper (Cu), but whether they contribute to nutritional immunity by influencing Zn and/or Cu availability has not been examined. We hypothesised that histatin-5 (Hst5) limits Zn availability (and promotes bacterial Zn starvation) and/or raises Cu availability (and promotes bacterial Cu poisoning). To test this hypothesis, Group A Streptococcus (GAS), which colonises the human oropharynx, was used as a model bacterium. Contrary to our hypothesis, Hst5 did not strongly influence Zn availability. This peptide did not induce expression of Zn uptake genes in GAS, nor did it suppress growth of an ΔadcAI mutant strain that is impaired in Zn uptake. Equilibrium competition measurements confirmed that Hst5 binds Zn weakly and does not compete with the high-affinity Zn uptake protein AdcAI for binding Zn. By contrast, Hst5 bound Cu with a high affinity and strongly influenced Cu availability. However, contrary to our hypothesis, Hst5 did not promote Cu toxicity. Instead, this peptide suppressed expression of Cu-inducible genes in GAS, stopped intracellular accumulation of Cu, and rescued growth of a ΔcopA mutant strain that is impaired in Cu efflux in the presence of added Cu. These findings led us to propose a new role for Hst5 and salivary histatins as major Cu buffers in saliva that reduce the potential negative effects of Cu exposure to microbes. We speculate that histatins promote oral and oropharyngeal health by contributing to microbial homeostasis in these host niches.