Host Cell Research Articles

Exploring the Interplay between Nutrients, Bacteriophages, and Bacterial Lipases in Host- and Bacteria-mediated Pathogenesis.

Pathogenic bacteria and host cells counteract or neutralize each other's effect in two fundamental ways: Direct invasion and secretion of various substances. Among these, lipases secreted by pathogenic bacteria and host cell lysozyme are key actors. Secreted lipases from pathogenic bacterial are suggested as a key player in the pathogen-host interaction. Among the gut microbial energy sources, glucose and fats have been referred to as one of the best inducers and substrates for bacterial lipases. Enrichment of bacterial growth medium with extra glucose or oil has been shown to induce lipase production in pathogenic bacteria. More recently, research has focused on the role of human gut phage alterations in the onset of dysbiosis because the bacteria-phage interactions can be dramatically affected by the nutrient milieu of the gut. However, the reciprocal role of bacterial lipases and phages in this context has not been well studied and there is no data available about how high glucose or fat availability might modulate the cellular milieu of the pathogenic bacteria-phageeukaryotic host cell interface. The purpose of this study was to evaluate the immunologic outcome of pathogenic bacteria-phage interaction under normal, high glucose, and high butter oil conditions to understand how nutrient availability affects lipase activity in pathogenic bacteria and, ultimately, the eukaryotic host cell responses to pathogenic bacteria-phage interaction. 10 groups of co-cultured T84 and HepG2 cells were treated with Pseudomonas aeruginosa strain PAO1 (P.a PAO1) in the presence and absence of its KPP22 phage and incubated in three different growth media (DMEM, DMEM + glucose and DMEM + butter oil). Structural and physiological (barrier function and cell viability), inflammatory (IL-6 and IL-8), metabolic (glucose and triglycerides), and enzymatic (lipases and lysozyme) parameters were determined. Excess glucose or butter oil enhanced additively extracellular lipase activity of P.a PAO1. Excess glucose or butter oil treatments also magnified P. a PAO1- induced secretion of inflammatory signal molecules (IL-1β, IL-6) from co-cultured cells, concomitant with the enhancement of intracellular triglycerides in co-cultured HepG2 cells, these effects being abolished by phage KPP22. The results of the present study imply that KPP22 phage influences the interplay between food substances, gut bacterial lipases, and the gut cellular milieu. This can be applied in two-way interaction: by affecting the microbial uptake of excess free simple sugars and fats from the gut milieu leading to decreased bacterial lipases and by modulating the immune system of the intestinal -liver axis cells. Further studies are needed to see if the biological consequences of these effects also occur in vivo.

Prediction of SARS-CoV-2 Infection Phosphorylation Sites and Associations of these Modifications with Lung Cancer Development.

Since the emergence of SARS-CoV-2 viruses, multiple mutant strains have been identified. Infection with SARS-CoV-2 virus leads to alterations in host cell phosphorylation signal, which systematically modulates the immune response. Identification and analysis of SARS-CoV-2 virus infection phosphorylation sites enable insight into the mechanisms of viral infection and effects on host cells, providing important fundamental data for the study and development of potent drugs for the treatment of immune inflammatory diseases. In this paper, we have analyzed the SARS-CoV-2 virus-infected phosphorylation region and developed a transformer-based deep learning-assisted identification method for the specific identification of phosphorylation sites in SARS-CoV-2 virus-infected host cells. Furthermore, through association analysis with lung cancer, we found that SARS-CoV-2 infection may affect the regulatory role of the immune system, leading to an abnormal increase or decrease in the immune inflammatory response, which may be associated with the development and progression of cancer. We anticipate that this study will provide an important reference for SARS-CoV-2 virus evolution as well as immune-related studies and provide a reliable complementary screening tool for anti-SARS-CoV-2 virus drug and vaccine design.

Amidst Cytokine Storm in Metabolic Diseases: Can 2-deoxy-D-glucose (2-DG) Cure COVID-19?

Abstract: The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pandemic disease COVID-19, which began in China in 2019, became the leading cause of fatalities globally. The transmission rate of the virus is directly proportional to the so-called ‘dance dynamic’ energy of the spike protein as this phenomenon favours the ligand-receptor binding. The clinical spectrum of the COVID-19 disease, which includes (inflammation, cytokine storm, and multi-organ dysfunction), puts Corona Warriors active in various aspects of the disease, such as the efficient management of critically ill COVID-19 patients, in danger of losing their lives. Due to its effects on an ancient oxygen-independent glycolytic pathway, anti-inflammatory properties, and competitive interaction with viral proteins, 2-deoxy-D-glucose (2-DG), which is being developed in India at the Defence Research and Development Organization (DRDO), has emerged as a ground-breaking agent for COVID-19 treatment. After a virus gains entry into host cells, it is found that metabolic reprogramming takes place to meet the nutritional and energy requirements for virus reproduction. The recent approval of 2-DG for adjunctive emergency usage by the Drug Controller General of India (DCGI) may mark a turning point in the management of mild to moderate COVID-19 infection.

Structure, Function, and Physicochemical Properties of Pore-forming Antimicrobial Peptides.

Antimicrobial peptides (AMPs), a class of antimicrobial agents, possess considerable potential to treat various microbial ailments. The broad range of activity and rare complete bacterial resistance to AMPs make them ideal candidates for commercial development. These peptides with widely varying compositions and sources share recurrent structural and functional features in mechanisms of action. Studying the mechanisms of AMP activity against bacteria may lead to the development of new antimicrobial agents that are more potent. Generally, AMPs are effective against bacteria by forming pores or disrupting membrane barriers. The important structural aspects of cytoplasmic membranes of pathogens and host cells will also be outlined to understand the selective antimicrobial actions. The antimicrobial activities of AMPs are related to multiple physicochemical properties, such as length, sequence, helicity, charge, hydrophobicity, amphipathicity, polar angle, and also self-association. These parameters are interrelated and need to be considered in combination. So, gathering the most relevant available information will help to design and choose the most effective AMPs.

Hydrogen sulfide: physiological roles and therapeutic implications against COVID-19.

The COVID-19 pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) poses a major menace to economic and public health worldwide. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) are two host proteins that play an essential function in the entry of SARS-COV-2 into host cells. Hydrogen sulfide (H2S), a new gasotransmitter, has been shown to protect the lungs from potential damage through its anti-inflammatory, antioxidant, antiviral, and anti-aging effects. It is well known that H2S is crucial in controlling the inflammatory reaction and the pro-inflammatory cytokine storm. Therefore, it has been suggested that some H2S donors may help treat acute lung inflammation. Furthermore, recent research illuminates a number of mechanisms of action that may explain the antiviral properties of H2S. Some early clinical findings indicate a negative correlation between endogenous H2S concentrations and COVID-19 intensity. Therefore, reusing H2S-releasing drugs could represent a curative option for COVID-19 therapy.

The Potential Role of Virus Infection in the Progression of Thyroid Cancer.

Multiple factors have engaged in the progression of thyroid cancer (TC). Recent studies have shown that viral infection can be a critical factor in the pathogenesis of TC. Viruses, such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may play an essential role in the occurrence, development, and even prognosis in TC. This review mainly explored the potential role of viral infection in the progress of TC. The possible mechanisms could be recognizing the host cell, binding to the receptors, affecting oncogenes levels, releasing viral products to shape a beneficial environment, interacting with immune cells to induce immune evasion, and altering the pituitary-thyroid axis. Thus, comprehensive knowledge may provide insights into finding molecular targets for diagnosing and treating virus-related TC.

Molecular docking and dynamics simulation reveal withanolides as potent antivirals against dengue virus

The prevalence of dengue remains a significant global threat to public health with millions of infections reported annually due to the lack of effective treatment options. Natural resources such as plants contain phytochemicals with desirable therapeutic effects. For instance, the Indian ginseng, Withania somnifera L. (Solanaceae), contains steroidal lactones, saponins, glycosides, and alkaloids which possessed antiviral activities against various viruses. In this study, docking analysis of seven compounds and phytochemicals were performed against the structural and non-structural (NS) proteins of all four dengue virus (DENV) serotypes as well as host cell receptors such as DC-SIGN and CLEC5A. Withanolide A (L5) was selected as the best inhibitor with high binding affinities towards ten targets consisting of DENV structural and NS proteins as well as the CLEC5A receptor. L5 also showed a fair stability with DENV1, DENV2, and DENV3 over a time span of 100 ns via molecular dynamics simulation. L5 demonstrated good drug-likeness properties, a moderate bioavailability score of 0.55, and is predicted to have high gastrointestinal absorptivity. The data from this in silico study revealed the potential of withanolide A to be further developed as an antiviral against dengue. This is the first study to report the in silico analyses of phytochemicals derived from W. somnifera L. (Solanaceae) against the viral proteins of DENV1 to 4 and their respective host cell receptors.

In Silico Design and Evaluation of a Novel Therapeutic Agent Against the Spike Protein as a Novel Treatment Strategy for COVID-19 Treatment.

Coronavirus disease 2019 (COVID-19) is a viral respiratory disease that is associated with severe damage to other human organs. It causes by a novel coronavirus, and it is spreading all over the world. To date, there is some approved vaccine or therapeutic agent which could be effective against this disease. But their effectiveness against mutated strains is not studied completely. The spike glycoprotein on the surface of the coronaviruses gives the virus the ability to bind to host cell receptors and enter cells. Inhibition of attachment of these spikes can lead to virus neutralization by inhibiting viral entrance. In this study, we tried to use the virus entrance strategy against itself by utilizing virus receptor (ACE-2) in order to design an engineered protein consisting of a human Fc antibody fragment and a part of ACE-2, which reacts with virus RBD, and we also evaluated this interaction by computational methods and in silico methods. Subsequently, we have designed a new protein structure to bind with this site and inhibit the virus from attaching to its cell receptor, mechanically or chemically. Various in silico software, bioinformatics, and patent databases were used to retrieve the requested gene and protein sequences. The physicochemical properties and possibility of allergenicity were also examined. Three-dimensional structure prediction and molecular docking were also performed to develop the most suitable therapeutic protein. The designed protein consisted of a total of 256 amino acids with a molecular weight of 28984.62 and 5.92 as a theoretical isoelectric point. Instability and aliphatic index and grand average of hydropathicity are 49.99, 69.57 and -0.594, respectively. In silico studies can provide a good opportunity to study viral proteins and new drugs or compounds since they do not need direct exposure to infectious agents or equipped laboratories. The suggested therapeutic agent should be further characterized in vitro and in vivo.

Investigating the Influence of Gut Microbiota-related Metabolites in Gastrointestinal Cancer.

Gastrointestinal (GI) cancer is a major health concern due to its prevalence, impact on well-being, high mortality rate, economic burden, and potential for prevention and early detection. GI cancer research has made remarkable strides in understanding biology, risk factors, and treatment options. An emerging area of research is the gut microbiome's role in GI cancer development and treatment response. The gut microbiome, vital for digestion, metabolism, and immune function, is increasingly linked to GI cancers. Dysbiosis and alterations in gut microbe composition may contribute to cancer development. Scientists study how specific bacteria or microbial metabolites influence cancer progression and treatment response. Modulating the gut microbiota shows promise in enhancing treatment efficacy and preventing GI cancers. Gut microbiota dysbiosis can impact GI cancer through inflammation, metabolite production, genotoxicity, and immune modulation. Microbes produce metabolites like short-chain fatty acids, bile acids, and secondary metabolites. These affect host cells, influencing processes like cell proliferation, apoptosis, DNA damage, and immune regulation, all implicated in cancer development. This review explores the latest research on gut microbiota metabolites and their molecular mechanisms in GI cancers. The hope is that this attempt will help in conducting other relevant research to unravel the precise mechanism involved, identify microbial signatures associated with GI cancer, and develop targets.

Susceptibility to recombinant SARS-CoV-2 spike protein entry in the lungs of high-fat diet-induced obese mice.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Obesity is a major risk factor for the development of COVID-19. Angiotensin-converting enzyme 2 (ACE2) is an essential receptor for cell entry of SARS-CoV-2. The receptor-binding domain of the S1 subunit (S1-RBD protein) in the SARS-CoV-2 spike glycoprotein binds to ACE2 on host cells, through which the virus enters several organs, including the lungs. Considering these findings, recombinant ACE2 might be utilized as a decoy protein to attenuate SARS-CoV-2 infection. Here, we examined whether obesity increases ACE2 expression in the lungs and whether recombinant ACE2 administration diminishes the entry of S1-RBD protein into lung cells. We observed that high-fat diet-induced obesity promoted ACE2 expression in the lungs by increasing serum levels of LPS derived from the intestine. S1-RBD protein entered the lungs specifically through ACE2 expressed in host lungs and that the administration of recombinant ACE2 attenuated this entry. We conclude that obesity makes hosts susceptible to recombinant SARS-CoV-2 spike proteins due to elevated ACE2 expression in lungs, and this model of administering S1-RBD protein can be applied to new COVID-19 treatments.

Study of Serratia phages using virulence tests

One of the main tests in selection of therapeutic phages is studing their virulence. Because of high stability of lysogenic status of bacterial culture, as well as ability in some cases of horizontal transfer of prophages and antibiotic resistance factors, existence of the moderate phages in medical preparations may cause negative results. The Serratia phages were studied with two main tests in the present work: sowing effectiveness and range of lysis action, as well as phage reproductive capacity on the host cells irradiated with UV rays. The results obtained showed that sowing effectiveness of studied phages and range of action are quite high. Out of 14 clones of Serratia phages 11 were characterized with reproductive ability on the host strains inactivated by UV rays. The results of above experimental works and other earlier tests allowed us selecting the components of Serratia phages for the medical-preventive preparation.

Bacterial cell differentiation enables population level survival strategies.

Clonal reproduction of unicellular organisms ensures the stable inheritance of genetic information. However, this means of reproduction lacks an intrinsic basis for genetic variation, other than spontaneous mutation and horizontal gene transfer. To make up for this lack of genetic variation, many unicellular organisms undergo the process of cell differentiation to achieve phenotypic heterogeneity within isogenic populations. Cell differentiation is either an inducible or obligate program. Induced cell differentiation can occur as a response to a stimulus, such as starvation or host cell invasion, or it can be a stochastic process. In contrast, obligate cell differentiation is hardwired into the organism's life cycle. Whether induced or obligate, bacterial cell differentiation requires the activation of a signal transduction pathway that initiates a global change in gene expression and ultimately results in a morphological change. While cell differentiation is considered a hallmark in the development of multicellular organisms, many unicellular bacteria utilize this process to implement survival strategies. In this review, we describe well-characterized cell differentiation programs to highlight three main survival strategies used by bacteria capable of differentiation: (i) environmental adaptation, (ii) division of labor, and (iii) bet-hedging.

Sequence polymorphisms in the reovirus σ1 attachment protein modulate encapsidation efficiency and replication in mice.

Viral attachment proteins can serve multiple functions during viral replication, including attachment to host cells, cell entry and disassembly, and modulation of host immune responses. The relationship between viral attachment protein encapsidation efficiency and viral replication in cells and animals is poorly understood. We engineered and characterized a panel of reoviruses that differ in the capacity to encapsidate the σ1 attachment protein. We found that strains encapsidating σ1 with higher efficiency bind cells more avidly and replicate and spread more efficiently in mice relative to those encapsidating σ1 with lower efficiency. These results highlight a function for σ1 attachment protein capsid abundance in viral replication in cells and animals, which may inform future use of reovirus as an oncolytic therapeutic.

Unraveling the Microbiome–Human Body Axis: A Comprehensive Examination of Therapeutic Strategies, Interactions and Implications

This review scrutinizes the intricate interplay between the microbiome and the human body, exploring its multifaceted dimensions and far-reaching implications. The human microbiome, comprising diverse microbial communities inhabiting various anatomical niches, is increasingly recognized as a critical determinant of human health and disease. Through an extensive examination of current research, this review elucidates the dynamic interactions between the microbiome and host physiology across multiple organ systems. Key topics include the establishment and maintenance of microbiota diversity, the influence of host factors on microbial composition, and the bidirectional communication pathways between microbiota and host cells. Furthermore, we delve into the functional implications of microbiome dysbiosis in disease states, emphasizing its role in shaping immune responses, metabolic processes, and neurological functions. Additionally, this review discusses emerging therapeutic strategies aimed at modulating the microbiome to restore host–microbe homeostasis and promote health. Microbiota fecal transplantation represents a groundbreaking therapeutic approach in the management of dysbiosis-related diseases, offering a promising avenue for restoring microbial balance within the gut ecosystem. This innovative therapy involves the transfer of fecal microbiota from a healthy donor to an individual suffering from dysbiosis, aiming to replenish beneficial microbial populations and mitigate pathological imbalances. By synthesizing findings from diverse fields, this review offers valuable insights into the complex relationship between the microbiome and the human body, highlighting avenues for future research and clinical interventions.

NRF2-mediated regulation of lipid pathways in viral infection

The first line of defense against viral infection of the host cell is the cellular lipid membrane, which is also a crucial first site of contact for viruses. Lipids may sometimes be used as viral receptors by viruses. For effective infection, viruses significantly depend on lipid rafts during the majority of the viral life cycle. It has been discovered that different viruses employ different lipid raft modification methods for attachment, internalization, membrane fusion, genome replication, assembly, and release. To preserve cellular homeostasis, cells have potent antioxidant, detoxifying, and cytoprotective capabilities. Nuclear factor erythroid 2-related factor 2 (NRF2), widely expressed in many tissues and cell types, is one crucial component controlling electrophilic and oxidative stress (OS). NRF2 has recently been given novel tasks, including controlling inflammation and antiviral interferon (IFN) responses. The activation of NRF2 has two effects: it may both promote and prevent the development of viral diseases. NRF2 may also alter the host's metabolism and innate immunity during viral infection. However, its primary function in viral infections is to regulate reactive oxygen species (ROS). In several research, the impact of NRF2 on lipid metabolism has been examined. NRF2 is also involved in the control of lipids during viral infection. We evaluated NRF2's function in controlling viral and lipid infections in this research. We also looked at how lipids function in viral infections. Finally, we investigated the role of NRF2 in lipid modulation during viral infections.

Design of SARS-CoV-2 protein S peptides recognized by the most frequent HLA alleles in the Moroccan population using an immunoinformatics approach

Background The coronavirus disease 2019 (COVID-19) is an infectious disease, caused by the new coronavirus known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and exhibits diverse clinical outcomes and symptoms in infected individuals, emphasizing the need to investigate how human genetic diversity influences the virus’s impact. This study aims to employ in silico methods to identify epitopes capable of eliciting an immune response, focusing on the most prevalent HLA-I and HLA-II alleles in the Moroccan population. Methods Our research consisted in predicting peptide-binding affinities between the most prevalent HLA Class I and Class II alleles in the Moroccan population and SARS-CoV-2 spike glycoprotein (S protein) peptides of variants isolated from strains of Moroccan patients. We performed the same analyses for SARS-CoV-2 wild type S protein to assess the ability of these HLA alleles to interact with peptides in the presence or absence of SARS-CoV-2 mutations. Results In a broader sense, 12 distinct HLA Class I and Class II alleles in the Moroccan population have been identified as possibly interacting with 19 epitopes in the SARS-CoV-2 S protein. Findings of this study must be validated in both in vitro and in vivo models. Conclusions These data may help clarify the issue of host cell susceptibility and the outcome of SARS-CoV-2 infection, and may guide further research to uncover potential targets for the vaccination strategy.

Genome-wide CRISPR/Cas9 screen reveals JunB downmodulation of HIV co-receptor CXCR4

HIV-1 relies extensively on host cell machinery for replication. Identification and characterization of these host-virus interactions is vital to our understanding of viral replication and the consequences of infection in cells. Several prior screens have identified host factors important for HIV replication but with limited replication of findings, likely due to differences in experimental design and conditions. Thus, unidentified factors likely exist. To identify novel host factors required for HIV-1 infection, we performed a genome-wide CRISPR/Cas9 screen using HIV-induced cell death as a partitioning method. We created a gene knockout library in TZM-GFP reporter cells using GeCKOv2, which targets 19,050 genes, and infected the library with a lethal dose of HIV-1NL4-3. We hypothesized that cells with a knockout of a gene critical for HIV infection would survive while cells with a knockout of a non-consequential gene would undergo HIV-induced death and be lost from the population. Surviving cells were analyzed by high throughput sequencing of the integrated CRISPR/Cas9 cassette to identify the gene knockout. Of the gene targets, an overwhelming majority of the surviving cells harbored the guide sequence for the AP-1 transcription factor family protein, JunB. Upon the generation of a clonal JunB knockout cell line, we found that HIV-1NL4-3 infection was blocked in the absence of JunB. The phenotype resulted from downregulation of CXCR4, as infection levels were recovered by reintroduction of CXCR4 in JunB KO cells. Thus, JunB downmodulates CXCR4 expression in TZM-GFP cells, reducing CXCR4-tropic HIV infection.

Let’s open our eyes to the importance of vaginal microbiota. Correlation between dysbiosis and HPV infection: A review

Infections with the human papillomavirus (HPV) are one of the most common sexually transmitted diseases and are the main cause of precancerous changes and cervical cancer development. However, mere infection does not guarantee the development of disease or carcinogenesis. For this to occur, high-risk types of HPV must integrate into the host cell genome, transitioning into a persistent form of infection. Following the discovery of risk factors for HPV infection and factors predisposing infection to a persistent form, the number of studies investigating the correlation between vaginal dysbiosis and infection has significantly increased. Numerous studies document a significant association between the state of vaginal bacterial flora and HPV infection, leading to the development of plentiful studies on infection pathogenesis, risk factors, prevention, and treatment methods using bacteria. In this paper, based on recently published studies and current state of science knowledge, we will outline the topic of vaginal microbiome, emphasize the importance of bacteria inhabiting the vagina for human health, and identify the problem of changes in vaginal microflora. We would like to contribute to the dissemination of knowledge about the vaginal microbiome and general knowledge about taking care of its health. We will also summarize available treatment methods based on bacterial environment and discuss those methods for which research is currently underway or should be initiated.

Dissecting OGT’s TPR domain to identify determinants of cellular function

O-GlcNAc transferase (OGT) is an essential mammalian enzyme that glycosylates myriad intracellular proteins and cleaves the transcriptional coregulator Host Cell Factor 1 to regulate cell cycle processes. Via these catalytic activities as well as noncatalytic protein-protein interactions, OGT maintains cell homeostasis. OGT's tetratricopeptide repeat (TPR) domain is important in substrate recognition, but there is little information on how changing the TPR domain impacts its cellular functions. Here, we investigate how altering OGT's TPR domain impacts cell growth after the endogenous enzyme is deleted. We find that disrupting the TPR residues required for OGT dimerization leads to faster cell growth, whereas truncating the TPR domain slows cell growth. We also find that OGT requires eight of its 13 TPRs to sustain cell viability. OGT-8, like the nonviable shorter OGT variants, is mislocalized and has reduced Ser/Thr glycosylation activity; moreover, its interactions with most of wild-type OGT's binding partners are broadly attenuated. Therefore, although OGT's five N-terminal TPRs are not essential for cell viability, they are required for proper subcellular localization and for mediating many of OGT's protein-protein interactions. Because the viable OGT truncation variant we have identified preserves OGT's essential functions, it may facilitate their identification.

Periodontopathogen-Related Cell Autophagy-A Double-Edged Sword.

The periodontium is a highly organized ecosystem, and the imbalance between oral microorganisms and host defense leads to periodontal diseases. The periodontal pathogens, mainly Gram-negative anaerobic bacteria, colonize the periodontal niches or enter the blood circulation, resulting in periodontal tissue destruction and distal organ damage. This phenomenon links periodontitis with various systemic conditions, including cardiovascular diseases, malignant tumors, steatohepatitis, and Alzheimer's disease. Autophagy is an evolutionarily conserved cellular self-degradation process essential for eliminating internalized pathogens. Nowadays, increasing studies have been carried out in cells derived from periodontal tissues, immune system, and distant organs to investigate the relationship between periodontal pathogen infection and autophagy-related activities. On one hand, as a vital part of innate and adaptive immunity, autophagy actively participates in host resistance to periodontal bacterial infection. On the other, certain periodontal pathogens exploit autophagic vesicles or pathways to evade immune surveillance, therefore achieving survival within host cells. This review provides an overview of the autophagy process and focuses on periodontopathogen-related autophagy and their involvements in cells of different tissue origins, so as to comprehensively understand the role of autophagy in the occurrence and development of periodontal diseases and various periodontitis-associated systemic illnesses.