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Host factors versus virulence-associated bacterial characteristics in neonatal and infantile bacteraemia and meningitis caused by Escherichia coli.

Possession of P fimbriae, virulence-associated O and K antigens, haemolysin and aerobactin production, and susceptibility to 10 antimicrobial agents were studied in 63 Escherichia coli strains isolated from blood or CSF of infants who were grouped according to their clinical characteristics. These isolates were compared with 35 faecal E. coli strains from healthy infants. Individual virulence factors showed a relatively weak association with invasive infection except for P fimbriae in urosepsis and aerobactin production in meningitis. Combinations of factors were generally more predictive for defining virulent clones, particularly in infants defined as being at normal risk of developing septicaemia. Thus, 62% of isolates from such infants had characteristics typical of previously described uropathogenic or meningitis-associated clones of E. coli, compared with 32% of the isolates from high-risk infants (i.e., those defined as being at high risk of developing septicaemia) and only 9% of the faecal isolates (p less than 0.001 and less than 0.05, respectively). Overall, 45% of the episodes of invasive infection were caused by such clones, whereas risk factors (conditions considered to be associated with increased risk of invasive infection) were present in 59% of the infected infants (39% in meningitis and urosepsis, 78% in cryptogenic septicaemia and untreated bacteraemia). The results indicated that bacterial factors played a significant causative role in neonatal meningitis and urosepsis, particularly in normal-risk infants, whereas predisposing host factors contributed greatly to cryptogenic septicaemia and untreated bacteraemia.

Antigens, Bacterial

Proximity interactome of alphavirus replicase component nsP3 includes proviral host factors eIF4G and AHNAK.

All positive-strand RNA viruses replicate their genomes in association with modified intracellular membranes, inducing either membrane invaginations termed spherules, or double-membrane vesicles. Alphaviruses encode four non-structural proteins nsP1-nsP4, all of which are essential for RNA replication and spherule formation. To understand the host factors associated with the replication complex, we fused the efficient biotin ligase miniTurbo with Semliki Forest virus (SFV) nsP3, which is located on the cytoplasmic surface of the spherules. We characterized the proximal proteome of nsP3 in three cell lines, including cells unable to form stress granules, and identified >300 host proteins constituting the microenvironment of nsP3. These included all the nsPs, as well as several previously characterized nsP3 binding proteins. However, the majority of the identified interactors had no previously identified roles in alphavirus replication, including 39 of the top 50 interacting proteins. The most prominent biological processes involving the proximal proteins were nucleic acid metabolism, translational regulation, cytoskeletal rearrangement and membrane remodeling. siRNA silencing confirmed six novel proviral factors, USP10, AHNAK, eIF4G1, SH3GL1, XAB2 and ANKRD17, which are associated with distinct cellular functions. All of these except SH3GL1 were also important for the replication of chikungunya virus. We discovered that the small molecule 4E1RCat, which inhibits the interaction between the canonical translation initiation factors eIF4G and eIF4E, exhibits antiviral activity against SFV. Since the same molecule was previously found to inhibit coronaviruses, this suggest the possibility that translation initiation factors could be considered as targets for broadly acting antivirals.

Viral Nonstructural Proteins

Host factors and breast cancer growth characteristics.

The rate of growth and spread of breast cancer varies considerably from patient to patient. An observational study was undertaken to identify possible associations between breast cancer growth characteristics and a wide variety of host factors, including demographic, anthropometric, hormonal and dietary variables in 91 patients with breast cancer. Increasing age was associated with favourable growth characteristics, while previous tonsillectomy was associated with adverse growth characteristics. There were no significant associations in anthropometric variables. For postmenopausal women, increasing bioavailability of oestradiol was associated with favourable growth characteristics, while increasing prolactin concentration was associated with adverse growth characteristics. Increasing consumption of sugar, fibre, fruit and vegetables and vitamins was associated with favourable growth characteristics. Consumption of fat (monounsaturated and saturated) was associated with adverse characteristics when adjustment was made for total energy intake. The host environment may play a role in the control of breast cancer growth. In particular, the associations with oestrogen and progesterone receptor status indicate that nutrients may be of value as biological response modifiers in patients having hormonal therapy. This requires further investigation to assess therapeutic potential.

Age Factors

The sialylation of gonococcal lipopolysaccharide by host factors: a major impact on pathogenicity.

The resistance of gonococci in most patients to complement mediated killing by human serum is due to sialylation of their lipopolysaccharide (LPS) which prevents bactericidal antibody from reacting with target sites. Two of the host factors responsible are: cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA), a well-known sialylating agent, and another factor which enhances the transfer of sialyl groups from CMP-NANA to LPS catalysed by a gonococcal sialyltransferase. The bacterial determinant of resistance is a conserved LPS component of about 4.5 kDa which is sialylated at a terminal Gal beta 1-4GlcNAc site on its side chain. The sialylated LPS forms a surface coat which is stainable by ruthenium red and connected with previously described 'capsules'. These observations sparked off an explosion of research. Recent publications show that sialylation of LPS by CMP-NANA affects additional important aspects of gonococcal pathogenicity, notably interactions with antibodies and phagocytes, and rendering the gonococcal surface more 'host-like'. Also, the observations have prompted an examination of LPS from some other pathogens for the presence of sialyl groups with positive results for Neisseria meningitidis and Haemophilus influenzae.

Antibodies, Bacterial

Viral attributes and host factors in carcinogenesis: herpesviruses.

This paper describes two different experiments of nature: 1) the persistence of unusual virus strains of Epstein-Barr virus (EBV) (which proved oncogenic in vitro) and cytomegalovirus (CMV) in lymphoid cells following congenital or early acquired infection; 2) the occurence of multiple cases of Burkitt's lymphoma and nasopharyngeal carcinoma in one family. All the members of this family were EBV viral capsid antigen (VCA) and nuclear antigen (EBNA) antibody positive. The two patients with nasopharyngeal carcinoma had high titers of EBV-VCA, EA, and EBNA antibodies. The only member of this family having EBV early antigen (EA antibodies in addition to the patients with tumors was the mother. Borderline IgA deficiency was documented in 3 members of this family. These findings illustrate the importance of host factors (intracellular resistance to transformation and secondarily, immunological surveillance) in the outcome of the host-virus challenge whether cancer or infectious disease is the outcome. Extensive studies of these cases may provide the best insight into the mysteries of viral oncogenesis.

Antibodies, Viral

Viral and host factors associated with SARS-CoV-2 disease severity in Georgia, USA.

While SARS-CoV-2 vaccines have shown strong efficacy, the continued emergence of new viral variants raises concerns about the ongoing and future public health impact of COVID-19, especially in locations with suboptimal vaccination uptake. We investigated viral and host factors, including vaccination status, that were associated with SARS-CoV-2 disease severity in a setting with low vaccination rates. We analyzed clinical and demographic data from 1,957 individuals in the state of Georgia, USA, coupled with viral genome sequencing from 1,185 samples. We found no specific mutations associated with disease severity. Compared to those who were unvaccinated, vaccinated individuals experienced less severe SARS-CoV-2 disease, and the effect was similar for both variants. Vaccination within the prior 3-9 months was associated with decreased odds of moderate disease, severe disease, and death. Older age and underlying health conditions, especially immunosuppression and renal disease, were associated with increased disease severity. Overall, this study provides insights into the impact of vaccination status, variants/mutations, and clinical factors on disease severity in SARS-CoV-2 infection when vaccination rates are low. Understanding these associations will help refine and reinforce messaging around the crucial importance of vaccination in mitigating the severity of SARS-CoV-2 disease.

Humans

Use of host factors to identify people at high risk for cutaneous malignant melanoma .

OBJECTIVE: To determine which host characteristics are risk factors for cutaneous malignant melanoma in order to aim prevention and early detection programs at people at high risk. DESIGN: Case-control study. SETTING: Southern Ontario. SUBJECTS: The 583 case subjects were aged 20 to 69 years and had had malignant melanoma newly diagnosed between Oct. 1, 1984, and Sept. 30, 1986. The 608 control subjects were randomly selected from a list of residents in the study area and were stratum matched for age, sex and municipality. INTERVENTION: Through in-person interviews the interviewer ascertained exposure to putative external risk factors and assessed skin colour and number of nevi on the arm, and the subject reported his or her natural hair colour at age 20 years, eye colour, skin reaction to repeated sun exposure, and freckle and whole-body nevus densities. RESULTS: Although all the host factors mentioned were significantly associated with melanoma risk when considered separately, only hair colour, skin reaction to repeated sun exposure, and self-reported freckle and nevus densities remained significant after backward logistic regression analysis. The odds ratio for melanoma was estimated to be 10.7 in people who had many nevi compared with those who had none (95% confidence interval [CI] 6.6 to 17.4), 4.0 in people who had red hair compared with those who had black hair (95% CI 1.9 to 8.2), 1.9 in people who had many freckles compared with those who had none or few (95% CI 1.3 to 2.8) and 1.4 respectively in people who burned and had a subsequent increase in tan and those who burned and had no increase in tan after repeated sun exposure compared with those who did not burn [corrected]. CONCLUSIONS: Four risk factors for malignant melanoma have been identified. Prospective evaluation of their predictive value should be done. In the meantime, however, these factors should be used to identify people apparently at high risk for malignant melanoma, who can then be targeted for early detection and prevention programs.

Adult

Host factors in lung cancer risk: a review of interdisciplinary studies.

Host-specific factors influence risk for lung cancer. A few case-control and family studies of lung cancer susceptibility allowed for known lung cancer carcinogens and showed strong familial clustering with some evidence for a codominantly acting major gene. Cytochrome P-450 enzymes (e.g., CYP1A1) activate many carcinogens in tobacco smoke but have shown inconsistent associations with risk for lung cancer. Case-control studies that assess the effects of CYPIID6 on lung cancer risk have consistently shown a mildly decreased risk for lung cancer among poor metabolizers. Cell surface markers have shown little relation to risk for lung cancer. Studies involving DNA or hemoglobin adducts, sister chromatid exchange, or oncogene activation only indirectly measure host-specific risk, and these assays have suffered from poor reproducibility and high cost. We describe epidemiological designs to assess specific genetic factors that may alter lung cancer risk.

Biomarkers

Host factors and susceptibility to influenza A infection: the effect of ABO blood groups and HL-A antigens.

The effect of two host genetic factors on the outcome of influenza A infections has been examined, ABO blood groups and HL-A antigens. A significantly higher proportion of blood group B subjects was found to have serological evidence of infection with epidemic influenza despite a high incidence of residual antibody among the volunteers. No difference was observed in the ability of subjects of different blood groups to seroconvert after receiving two doses of live attenuated influenza A vaccine, but a significantly higher proportion of blood group A vaccines seroconverted after receiving their first dose of vaccine. The association between HL-A type BW16 and resistance to infection with influenza could not be confirmed. The results are discussed in terms of an indirect association between susceptibility to influenza infection and the two host genetic factors.

ABO Blood-Group System

A host factor absent from Lactococcus lactis subspecies lactis MG1363 is required for conjugative transposition.

In matings between Lactococcus lactis strains, the conjugative transposons Tn916 and Tn919 are found in the chromosome of the transconjugants in the same place as in the chromosome of the donor, indicating that no transposition has occurred. In agreement with this, the frequency of L. lactis transconjugants from intraspecies matings is the same whether the donor contains the wild-type form of the transposon or the mutant Tn916-int1, which has an insertion in the transposon's integrase gene. However, in intergeneric crosses with Bacillus subtilis or Enterococcus faecalis donors, Tn916 and Tn919 transpose to different locations on the chromosome of the L. lactis transconjugants. Moreover, Tn916 and Tn919 could not be transferred by conjugation from L. lactis and B. subtilis, E. faecalis or Streptococcus pyogenes. This suggests that excision of these elements does not occur in L. lactis. When cloned into E. coli with adjacent chromosomal DNA from L. lactis, the conjugative transposons were able to excise, transpose and promote conjugation. Therefore, the inability of these elements to excise in L. lactis is not caused by a permanent structural alteration in the transposon. We conclude that L. lactis lacks a factor required for excision of conjugative transposons.

Bacillus subtilis

Supercoiling, integration host factor, and a dual promoter system, participate in the control of the bacteriophage lambda pL promoter.

The high level of efficiency of the bacteriophage lambda pL promoter is dependent upon the topological state of the promoter DNA and the binding of a DNA-bending protein, IHF, to a site centered -86 base-pairs upstream from the pL transcription start site. Abortive initiation assays indicate that DNA supercoiling stimulates open complex formation, whereas IHF enhances promoter recognition. IHF stimulates promoter recognition to the same extent on linear and supercoiled templates. We found that the pL region contains a second promoter, pL2, that initiates transcription 42 base-pairs upstream from pL. Although competitive with pL and inhibited by IHF, mutations in pL2 do not affect the regulation of pL. Stimulation by IHF is helix-face-dependent. IHF inhibits pL when the IHF binding site is displaced a helical half-turn upstream. The pL sequences protected against DNase I digestion by bound IHF and RNA polymerase do not overlap. However, DNase I-hypersensitive sites appear in the region between the two bound proteins. In addition, IHF enhances RNA polymerase binding to pL. These data suggest that stimulation of pL by IHF involves the interaction of IHF and RNA polymerase to form a loop or otherwise distort the DNA between their binding sites.

Bacterial Proteins

Host factors and acute lower respiratory infections in pre-school children.

The relationship between certain host-related variables and the short-term outcome of hospitalization for severe acute lower respiratory infections was studied prospectively in a cohort of 103 pre-school Nigerian children. The respective mean ages of those with bronchiolitis and croup were 3.2 months and 18.9 months while the corresponding M:F ratios were 2.5:1 and 1:1. It was highly significant that all the eight children that died were malnourished (P less than 0.01). Furthermore, malnourished subjects with pleural effusion, in whom bacteraemia was common, stayed longest in hospital while subjects with bronchiolitis and croup, in whom malnutrition was distinctly uncommon, had the shortest duration of admission. Multiple microbial identifications and bacteraemia were common in malnourished subjects with ALRI. Mortality was significantly higher in older children (P less than 0.05), but sex, immunization/breast-feeding status and co-existing measles or pertussis, were individually neither related to the admission outcome nor the duration. It is concluded that malnutrition is a strong predictor of ALRI-related death in the pre-school child. The significance of bacteraemia and multiple microbial identifications in malnourished children, and the ARI-control implications of the study are discussed.

Acute Disease

[Host factors which influence the outcome of pneumonia in the elderly].

We examined 135 elderly patients with pneumonia to clarify the factors predicting on the outcomes of the elderly pneumonic patients. In the fatal cases respiratory symptoms such as cough and sputum, except for dyspnea were less frequent but pulmonary infiltrations on chest roentgenograms were more massive as compared with those in the survived cases. Thus, it was suggested that in the fatal cases the more advanced pneumonia had developed at the time when the diagnosis of pneumonia was made. The fatal cases showed hypoalbuminemia, hypocholesterolemia and hyponatlemia more frequently as compared with survived cases. Among these laboratory values, the decreased serum albumin concentration seemed to be most closely correlated with the fatal outcome of the elderly pneumonic patients. There were significant differences in the outcomes among three groups of the patients, those who were the prolonged bed-ridden, those with severe underlying diseases such as cancer and those treated as out-patients. The out patients showed the most favorable outcome and the prolonged bed-ridden patients the worst outcome. Approximately, 39% of the fatal cases were complicated with multiple organ failure. These results suggest that more important factors which affect the outcomes of pneumonia in the elderly may be not merely aging but the conditions of the host at onset of the disease.

Aged

Host factors in urinary infections.

To prevent the urologist from becoming simply a urinary tract mechanic we must develop more specific tests, perfect present tests and use these tests to elicit faulty mechanisms of host resistance of patients with urinary tract infections. We must then provide, from our research information, therapeutic measures to protect the faulty host from the inconvenience of recurrent significant bacteriuria and its sequelae.

Antibodies, Bacterial

Host factors associated with HIV-related oral candidiasis. A review.

Human immunodeficiency virus (HIV)-related oral candidiasis affects approximately one third of HIV-seropositive patients and more than 90% of patients with AIDS. It is necessary to identify patients who have a greater risk of candidiasis developing, so that interventions can be designed to reduce the frequency. This is particularly important because there is evidence that Candida species are immunosuppressive and therefore candidiasis may adversely affect the prognosis of patients with HIV. Susceptibility to HIV-related oral candidiasis is associated with xerostomia, severity of disease, depression of cell-mediated immunity, and older age (greater than 35 years). The frequency of HIV-related oral candidiasis is notably increased when the CD4 lymphocyte count falls to less than 300 cells/mm3. Xerostomia appears to be a better predictor of HIV-related oral candidiasis than CD4 count and should be prevented (e.g., by avoiding xerogenic drugs) and treated, when necessary, to minimize the risk of oral candidiasis.

Acquired Immunodeficiency Syndrome

AP2: an indispensable host factor in virus infection.

Adaptor protein complex 2 (AP2), a central regulator of clathrin-mediated endocytosis and intracellular cargo trafficking, is hijacked by numerous viruses to complete their infectious cycles. This review systematically synthesizes the multifaceted roles of AP2 across the entire viral life cycle, from entry and replication to assembly and release, as well as in immune evasion. By delineating how diverse viruses exploit this key host machinery, we further consolidate the rationale and current progress in developing broad-spectrum antiviral strategies that target AP2 and its regulatory pathways. This work aims to provide a unified perspective on AP2 as a critical host-pathogen interface, offering new insights into viral pathogenesis and antiviral drug discovery.

Humans

Host factors in the susceptibility of rheumatic patients to streptococcal infections.

In children and adolescents who each had at least one previous episode of rheumatic fever and who were not maintaining effective anti-streptococcal prophylaxis, the attack rates of subsequent streptococcal infections declined with advancing age, but were unaffected by gender, cardiac status, or multiplicity of antecedent rheumatic episodes. The rate of rheumatic recurrence per streptococcal infection fell with advancing age, but rose with increasing amounts of cardiac damage and with multiplicity of previous rheumatic attacks. The results suggest that the underlying clinical features of the host have a greater effect on the rheumatogenicity of an acquired streptococcal infection than on the ability to avoid the infection.

Acute Disease