SEARCH · PubMed Health

Results for “Variant”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources

PubMed2000

Structure of the human serotonin 5-HT4 receptor gene and cloning of a novel 5-HT4 splice variant.

Several variants of the serotonin 5-HT4 receptor are known to be produced by alternative splicing. To survey the existence and usage of exons in humans, we cloned the human 5-HT4 gene. Based on sequence analysis seven C-terminal variants (a-g) and one internal splice variant (h) were found. We concentrated in this study on the functional characterization of the novel splice variant h, which leads to the insertion of 14 amino acids into the second extracellular loop of the receptor. The h variant was cloned as a splice combination with the C-terminal b variant; therefore, we call this receptor 5-HT4(hb). This novel receptor variant was expressed transiently in COS-7 cells, and its pharmacological profile was compared with those of the previously cloned 5-HT4(a) and 5-HT4(b) isoforms, with the latter being the primary reference for the h variant. In competition binding experiments using reference 5-HT4 ligands, no significant differences were detected. However, the broadly used 5-HT4 antagonist GR113808 discriminated functionally among the receptor variants investigated. As expected, it was an antagonist on the 5-HT4(a) and 5-HT4(b) variant but showed partial agonistic activity on the 5-HT4(hb) variant. These data emphasize the importance of variations introduced by splicing for receptor pharmacology and may help in the understanding of conflicting results seen with 5-HT4 ligands in different model systems.

Amino Acid Sequence↗

PubMed2003

Prevalence of HBV precore/core promoter variants in the United States.

Variants in the precore (G(1896)A) and core promoter (A(1762)T, G(1764)A) regions of hepatitis B virus (HBV) may be related to serum HBV DNA levels and severity of liver disease. The aims of this nationwide study were to determine the prevalence of HBV precore/core promoter variants in the United States and the association between these variants and patient demographics, HBV genotypes, serum HBV DNA level, and severity of liver disease. A total of 694 consecutive chronic HBV-infected patients seen in 17 U.S. liver centers during a 1-year period were enrolled. Demographic, clinical, and laboratory data were collected. Sera were tested for HBV genotypes as well as precore and core promoter variants by line-probe assays. Quantitative HBV DNA levels were determined using Cobas Amplicor HBV Monitor kits. Precore and core promoter variants were found in 27% and 44% of patients with chronic HBV infection in the United States. Precore and core promoter variants were more common in hepatitis B e antigen (HBeAg)-negative than in HBeAg-positive patients (precore, 38% vs. 9%; core promoter, 51% vs. 36%; respectively, P <.001). The prevalence of these variants was related to ethnicity, place of birth, and HBV genotypes. Patients with core promoter variants were more likely to have hepatic decompensation. Precore and/or core promoter variants were associated with higher serum HBV DNA levels in HBeAg-negative but not in HBeAg-positive patients. In conclusion, HBV precore and core promoter variants are not rare in the United States. Physicians should be aware of the existence of HBV precore and core promoter variants and the clinical condition of "HBeAg-negative chronic hepatitis."

Adult↗

PubMed1994

Expression and modulation of CD44 variant isoforms in humans.

CD44 is a ubiquitous surface molecule that exists as a number of isoforms, generated by alternative splicing of 10 "variant" exons. Little is known about the expression and function of the variant isoforms, except that certain isoforms may play a role in cancer metastasis. We produced mAbs against CD44 variant regions encoded by exons 4v, 6v, and 9v, by immunizing mice with a fusion protein spanning variant exons 3v to 10v. A comprehensive analysis of human tissues revealed that CD44 variant isoforms were expressed widely throughout the body, principally by epithelial cells. However there was differential expression of CD44 variant exons by different epithelia. Most epithelia expressed exon 9v, but much fewer expressed 6v or 4v. The regions of epithelia that expressed the highest levels of the variant isoforms were the generative cells, particularly the basal cells of stratified squamous epithelium, and of glandular epithelium. CD44 variant isoforms were also expressed differentially by leukocytes, with CD44-9v expressed at very low levels and CD44-6v and 4v virtually absent. However, CD44-9v and CD44-6v were the main variants that were transiently upregulated on T cells after mitogenic stimulation and on myelomonocytic cell lines by TNF alpha and IFN gamma treatment. Some epithelial cell lines could preferentially upregulate CD44-6v upon IFN gamma incubation. These results show that CD44 variant isoforms are expressed much more widely than first appreciated, and that expression of the variant isoforms on some cell types can be modulated by particular cytokines.

Amino Acid Sequence↗

PubMed1984

Growth control variant cell line having increased serum requirement and decreased response to platelet-derived growth factor: reversion by 5-azacytidine.

Variants of the mouse embryo fibroblast X melanoma hybrid clone 100A have been isolated by a procedure that selects against cells that are able to grow in medium containing low concentrations of serum plus insulin. Three variant clones derived from this selection were found to have a much higher serum requirement than the parental clone 100A cells, as evidenced by a very low rate of DNA synthesis and growth in medium containing low concentrations of serum. Two of the variants had approximately double the number of chromosomes as the parental cell line, while one had approximately the same number of chromosomes as the parental cells. One of the variants was very strongly reverted by 5-azacytidine but not by ethyl methanesulfonate, suggesting that it reverted by a nonmutational mechanism such as a stable change in DNA methylation. Analysis of the growth requirements in hormone-supplemented serum-free media of the 100A parent, the INS 471 variant, and revertants of the variant indicated that the variant had a specific deficiency in its growth response to platelet-derived growth factor (PDGF). PDGF dose-response curves obtained with the variant cells were shifted approximately an order of magnitude toward higher PDGF concentrations relative to PDGF dose-response curves obtained with the parental 100A cells. This quantitative increase in PDGF requirement of the INS 471 variant appears to explain the increased serum requirement of this variant. Equilibrium binding experiments performed with 125I-PDGF suggest that the variant does not have a decreased number of PDGF receptors.

Animals↗

PubMed1993

A tumor escape variant that has lost one major histocompatibility complex class I restriction element induces specific CD8+ T cells to an antigen that no longer serves as a target.

After loss of expression of a major histocompatibility complex class I Kk allele, the escape variant of an immunogenic tumor grows progressively in normal mice. This progressor variant is resistant to killing by cytotoxic T lymphocytes (CTLs) directed against the A and B antigens presented by Kk. Although the variant retains the expression of the Dk allele and is sensitive to CTLs directed against the C antigen presented by Dk, the variant failed to induce CTLs to this antigen in vivo. Instead, the variant induced CD8+ T cells directed to the A antigen. This was shown at the molecular level by T cell receptor beta chain sequence analysis of the responding cells. Further evidence for the presence of A antigen in the variant came from the finding that spleen cells of mice injected intraperitoneally with the variant tumor cells were primed for an anti-A CD8+ CTL response in vivo. Thus, in contrast to other variants that lost a target antigen and induced a CTL response to remaining target antigens, the Kk loss variant continued to induce an immune response to a tumor antigen that is no longer presented on the tumor cell surface. Even though the variant escapes in a single step because an effective CTL response to secondary antigens is prevented, these secondary antigens remain as potential targets of immunotherapy on the variant's cell surface.

Animals↗

PubMed2026

Interrogation of functional variants in COPD GWAS loci by massively parallel reporter assays.

RATIONALE: Genome-wide association study (GWAS) loci often contain many linked variants, making it difficult to determine which variant is functionally relevant. Massively parallel reporter assays (MPRA) allow experimental testing of candidate variants to identify those with regulatory activity. Prior chronic obstructive pulmonary disease (COPD) MPRA studies have largely focused on individual loci, whereas broader multi-locus, multi-cell-type interrogation remains limited. OBJECTIVES: We aim to identify functional variants in five COPD GWAS loci across three lung-relevant cell types. METHODS: We screened 1120 variants using MPRA in epithelial (16HBE), fibroblast (MRC5), and endothelial (HUVEC) cells followed by reporter assay validation. Public Hi-C, ChIP-seq and ATAC-seq datasets were analyzed to evaluate chromatin context near candidate variants. We further performed CRISPR interference (CRISPRi) targeting variant-containing regions and measured gene expression by RT-qPCR in primary normal human bronchial epithelial (NHBE) cells using two gRNAs per variant. Co-immunoprecipitation was performed to test interaction between selected candidate genes. MEASUREMENTS AND MAIN RESULTS: In MPRA, we identified 25 variants with allele-specific effects (∼2% of tested variants). Enrichment of H3K27Ac and open chromatin near rs35421223 was detected in 16HBE cells. CRISPRi identified two SNP-gene pairs, RUVBL1 and RAB7A regulated by rs35421223 in both the 16HBE cell line and primary NHBE cells. We detected interaction between RUVBL1 and the known COPD gene product FAM13A. CONCLUSIONS: Screening COPD loci across three cell types identified functional regulatory variants and linked them to candidate target genes for future mechanistic studies.

Journal Article↗

PubMed2025

Leveraging protein language models for cross-variant CRISPR/Cas9 sgRNA activity prediction.

MOTIVATION: Accurate prediction of single-guide RNA (sgRNA) activity is crucial for optimizing the CRISPR/Cas9 gene-editing system, as it directly influences the efficiency and accuracy of genome modifications. However, existing prediction methods mainly rely on large-scale experimental data of a single Cas9 variant to construct Cas9 protein (variants)-specific sgRNA activity prediction models, which limits their generalization ability and prediction performance across different Cas9 protein (variants), as well as their scalability to the continuously discovered new variants. RESULTS: In this study, we proposed PLM-CRISPR, a novel deep learning-based model that leverages protein language models to capture Cas9 protein (variants) representations for cross-variant sgRNA activity prediction. PLM-CRISPR uses tailored feature extraction modules for both sgRNA and protein sequences, incorporating a cross-variant training strategy and a dynamic feature fusion mechanism to effectively model their interactions. Extensive experiments demonstrate that PLM-CRISPR outperforms existing methods across datasets spanning seven Cas9 protein (variants) in three real-world scenarios, demonstrating its superior performance in handling data-scarce situations, including cases with few or no samples for novel variants. Comparative analyses with traditional machine learning and deep learning models further confirm the effectiveness of PLM-CRISPR. Additionally, motif analysis reveals that PLM-CRISPR accurately identifies high-activity sgRNA sequence patterns across diverse Cas9 protein (variants). Overall, PLM-CRISPR provides a robust, scalable, and generalizable solution for sgRNA activity prediction across diverse Cas9 protein (variants). AVAILABILITY AND IMPLEMENTATION: The source code can be obtained from https://github.com/CSUBioGroup/PLM-CRISPR.

CRISPR-Cas Systems↗

PubMedDate not supplied

Coronal imaging of the osteomeatal unit: anatomy of 24 variants.

The purpose of this paper is to present a user-friendly reference for 24 of the most common normal variants of the osteomeatal unit. A five image set of consecutive normal coronal hanging head computed tomography (CT) images was obtained. Half of each image was duplicated enough times to allow superimposition of the variants. For organizational purposes, each variant was sorted into six color-coded regions: middle turbinate (five variants), inferior turbinate (three variants), maxillary sinus (three variants), nasal septum (three variants), ethmoid sinuses (five variants), and uncinate process (five variants). This reference can be used to rapidly identify a CT scan level and obtain an overview of common variants in that level. In addition, the color-coded system can be used to find any variant on all appropriate CT levels quickly by locating its colored column.

Humans↗

PubMed2006

Variants of human papillomavirus types 16 and 18: histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in cervical smear.

Human papillomavirus (HPV) genotypes cannot fully explain the histological diagnosis of women with glandular abnormalities detected by cervical smear. Thus, this study was designed to analyze the distribution of HPV-16 and HPV-18 variants in women referred because of atypical glandular cells and adenocarcinoma in situ in their cervical smears and its association with histological results. Twenty-four women with HPV-16 and 6 with HPV-18, selected from 160 women with cervical smears suggestive of glandular abnormalities, were included. Histological results showed cervicitis (1 case), squamous neoplasia (18 cases), glandular neoplasia (7 cases), and glandular neoplasia associated with a squamous component (4 cases). Among the 24 cases presenting HPV-16, the European variant was detected in 15 (62%) and the Asian American in 9 (38%). Among the 15 cases associated with the European variant, 14 (93%) presented squamous neoplasia and 1 (7%) invasive adenocarcinoma. Asian-American HPV-16 variants were significantly associated with histological diagnosis of glandular neoplasia alone (odds ratio, 9.3 [1.4-60.2]) or associated with squamous neoplasia (odds ratio, 18.7 [1.5-232.3]). Adenocarcinomas were detected in 4 of 6 HPV-18-positive cases, being 2 cases had the European variant, 1 had the Asian Amerindian variant, and 1 had the African variant. The association of HPV-16 with squamous or glandular neoplasia is explained by its variants. In this study, squamous neoplasia was related to the European variant of HPV-16, whereas glandular neoplasia was related to the Asian-American variant. Glandular neoplasia is associated with HPV-18, but the results of our analysis of its variants were inconclusive.

Adenocarcinoma↗

PubMed1995

Identification of five allelic variants of the sheep PrP gene and their association with natural scrapie.

Scrapie is a fatal neurodegenerative disease of sheep that belongs to the group of prion diseases found in humans and animals. The host encoded prion protein (PrP) plays a central role in the disease process. In the PrP genes of man, mice and sheep, polymorphisms have been found that are associated with disease susceptibility and pathogenesis. We have used denaturing gradient gel electrophoresis (DGGE) to detect polymorphisms in the sheep PrP gene. In addition to the already described polymorphisms at codons 136, 154 and 171, we identified a hitherto unknown G --> T transition at codon 171. This transition is responsible for a glutamine to histidine substitution. An arginine to glutamine substitution at this position has been described previously. DGGE allowed us to identify five different combinations of these polymorphisms within the PrP gene representing five allelic variants, which were cloned and sequenced. Based on the triplet sequences present at codons 136, 154 and 171 these allelic variants were designated PrPVRQ, PrPARR, PrPARQ, PrPARH and PrPAHQ. To determine the association of these allelic variants with natural scrapie, we screened 34 scrapie affected and 91 healthy control sheep of the Texel breed for the presence of these allelic variants. In these two groups, the five variants gave rise to 13 different genotypes. The distribution of the allelic variants among both groups showed marked differences. The PrPVRQ variant was present with high frequency in scrapie affected sheep, whereas the PrPARR variant was almost exclusively present in the healthy group. Two other variants, PrPARQ and PrPARH, were found in both groups with equal frequencies. The data obtained suggest modulation of disease susceptibility in these Texel sheep by at least five different PrP allelic variants, with the PrPVRQ and PrPARR alleles acting in a dominant, but opposite fashion over the PrPARQ and PrPARH alleles. The frequency of the PrPAHQ variant was too low to draw any conclusions.

Alleles↗

PubMed2006

Variants of Peach latent mosaic viroid inducing peach calico: uneven distribution in infected plants and requirements of the insertion containing the pathogenicity determinant.

Previous characterization of Peach latent mosaic viroid (PLMVd) variants from a single peach calico (PC) isolate showed that PC symptoms are induced by variants with a 12-13 nt insertion at a specific position and folding into a hairpin with a U-rich loop. Here, this study was extended to two other PC isolates. PLMVd variants with insertions similar to those reported previously (type 1), predominated in one isolate (PC-P2). The second (PC-P1), in addition to these variants, contained others with insertions in the same position and of the same size, but with the hairpin capped by a GA-rich loop (type 2). When symptomatic and non-symptomatic tissues from both isolates were used to inoculate GF-305 peach seedlings, they reproduced the phenotype of the inoculum source, indicating that variants differing in pathogenicity are unevenly distributed within single plants. Moreover, characterization of the progeny from inoculations with the PC-P1 source showed that variants with insertions of type 1 and 2 were predominant in the symptomatic and non-symptomatic seedlings, respectively, confirming the association between PC and variants with type 1 but not type 2 insertions. Inoculations with dimeric in vitro transcripts from PLMVd variants with type 1, type 2 and with a chimeric insertion showed that the variant with type 2 insertion was latent and established that the U-rich capping loop has a major role in PC, although the adjacent stem may also have some influence. Insertions can be acquired and lost during infection, suggesting that latent variants can evolve into pathogenic variants and vice versa.

Genetic Variation↗

PubMed2025

Defining and cataloging variants in pangenome graphs.

Structural variation causes some human haplotypes to align poorly with the linear reference genome, leading to 'reference bias'. A pangenome reference graph could ameliorate this bias by relating a sample to multiple reference assemblies. However, this approach requires a new definition of a 'genetic variant.' We introduce a definition of pangenome variants and a method, pantree, to identify them. Our approach involves a pangenome reference tree which includes all nodes (sequences) of the pangenome graph, but only a subset of its edges; non-reference edges are variant edges. Our variants are biallelic and have well-defined positions. Analyzing the Minigraph-Cactus draft human pangenome reference graph, we identified 29.6 million genetic variants. Most variants (99.2%) are small, and most small variants (73.9%) are SNPs. 3.5 million variants (11.7%) have a reference allele which is not on GRCh38; these variants are difficult to detect without a pangenome reference, or with existing pangenome-based approaches. They tend to be embedded within tangled, multiallelic regions. We analyze two medically relevant regions, around the HLA-A and RHD genes, identifying thousands of small variants embedded within several large insertions, deletions, and inversions. We release an open-source software tool together with a VCF variant catalogue.

Journal Article↗

PubMedDate not supplied

Molecular variants of human papillomavirus type 16 and risk for cervical neoplasia in South Africa.

Non-European variants of human papillomavirus (HPV) type 16 are generally associated with a greater risk of cervical neoplasia than European prototype variants. We investigated whether this association would persist in a population in which non-European HPV 16 variants were more common. We sequenced HPV 16 isolates in cervical samples collected from 93 Black South African women enrolled in a cervical cancer screening study and examined associations between cervical neoplasia identified though colposcopy with cervical biopsy and the specific HPV 16 variant identified. The European prototype variant (EP) was the most commonly identified variant in this population (47% of all isolates), but African variants (Af-1 and Af-2) were also quite common (41% of all isolates). In contrast to previous studies, we found no evidence that non-European variants were associated with an increased risk of neoplasia. Rather, most of the HPV 16-associated cancers were found in association with EP (71% of 14 cases). In this setting where African HPV 16 variants were common, no increased risk for cervical neoplasia was found among women with these variants compared with other HPV 16 variants.

Adult↗

PubMed1994

[Formation of drug-induced serotype variants of Pseudomonas aeruginosa: changes in biochemical properties, drug susceptibility and outer membrane proteins].

The serotype variants were formed in some isolates of Pseudomonas aeruginosa in the presence of anti-pseudomonal drugs in vitro. Pyocin type, various biochemical properties and drug susceptibility of these variants were compared with those of the parent cells. Furthermore, the patterns of outer membrane proteins were also examined for some respective parent and variant cells by the SDS-PAGE and compared with their drug susceptibilities. In P. aeruginosa No. 1-S (serotype E) and No. 1-R (serotype C), simultaneously isolated from the identical specimen of the infectious patient, the serotype variants were formed by anti-pseudomonal drugs and accompanied by changes in pyocin types, some biochemical properties and susceptibilities to various kinds of anti-pseudomonal drugs. When the profiles of outer membrane proteins of P. aeruginosa No. 1-R parent and two variant cells were evaluated by the SDS-PAGE, the quantitative differences of the porin proteins between the parent and variant cells were well related to their drug susceptibilities. Although eight variant cells with other serotype were formed from the parent cells (serotype A) of P. aeruginosa No. 13, four variants with serotype M and one non-typable variant showed changes in drug susceptibility such as resistance to imipenem only and no changes in biochemical properties. On the other hand, three other variants showed marked changes in two kinds of biochemical properties and in susceptibilities to various kinds of anti-pseudomonal drugs. From the results of SDS-PAGE, it was found that the porin protein profiles of outer membranes of these parent and variant cells except a few cells which corresponded to their drug susceptibility.

Anti-Bacterial Agents↗

PubMed2007

Identification and functional characterization of genetic variants of human organic cation transporters in a Korean population.

Genetic variants of three human organic cation transporter genes (hOCTs) were extensively explored in a Korean population. The functional changes of hOCT2 variants were evaluated in vitro, and those genetic polymorphisms of hOCTs were compared among different ethnic populations. From direct DNA sequencing, 7 of 13 coding variants were nonsynonymous single-nucleotide polymorphisms (SNPs), including four variants from hOCT1 (F160L, P283L, P341L, and M408V) and three from hOCT2 (T199I, T201M, and A270S), whereas 6 were synonymous SNPs. The linkage disequilibrium analysis presented for three independent LD blocks for each hOCT gene showed no significant linkage among all three hOCT genes. The transporter activities of MDCK cells that overexpress the hOCT2-T199I, -T201M, and -A270S variants showed significantly decreased uptake of [(3)H]methyl-4-phenylpyridinium acetate (MPP(+)) or [(14)C]tetraethylammonium compared with those cells that overexpress wild-type hOCT2, and the estimated kinetic parameters of these variants for [(3)H]MPP(+) uptake in oocytes showed a 2- to 5-fold increase in K(m) values and a 10- to 20-fold decrease in V(max) values. The allele frequencies of the five functional variants hOCT1-P283L, -P341L, and hOCT2-T199I, -T201M, and -A270S were 1.3, 17, 0.7, 0.7, and 11%, respectively, in a Korean population; the frequency distributions of these variants were not significantly different from those of Chinese and Vietnamese populations. These findings suggest that genetic variants of hOCTs are not linked among three genes in a Korean population, and several of the hOCT genetic variants cause decreased transport activity in vitro compared with the wild type, although the clinical relevance of these variants remains to be evaluated.

1-Methyl-4-phenylpyridinium↗

PubMed1999

Effect of loss of DNA mismatch repair on development of topotecan-, gemcitabine-, and paclitaxel-resistant variants after exposure to cisplatin.

Loss of DNA mismatch repair (MMR) causes genomic instability by markedly increasing the frequency of sporadic mutations in both coding and noncoding sequences. Little is known about how loss of MMR affects sensitivity to the mutagenic effect of chemotherapeutic agents. We wanted to determine how loss of MMR affects the ability of cisplatin, a known mutagen, to generate human tumor cell variants resistant to other drugs with which cisplatin is commonly combined in treatment regimens. We compared the ability of cisplatin to produce variants resistant to topotecan, gemcitabine, and paclitaxel in two pairs of MMR-proficient and -deficient cells that included sublines of the human colon carcinoma cell line HCT-116 and sublines of the human endometrial adenocarcinoma cell line HEC59. Cells were exposed to increasing concentrations of cisplatin for 1 h, and the surviving population was tested for the frequency of variants resistant to these single molecular target drugs 10 days later. The frequency of variants increased linearly with cisplatin concentration for all three drugs. Cisplatin was 2.6 +/- 0.3- (S.D.), 3.6 +/- 0.9-, and 2.3 +/- 0.1-fold more potent at producing topotecan-, gemcitabine-, and paclitaxel-resistant variants in the MMR-deficient than in the MMR-proficient HCT116 cells (P <.05 for all). Cisplatin was 1.4 +/- 0.3- and 1.4 +/- 0.4-fold more potent at generating topotecan- and gemcitabine-resistant variants in MMR-deficient HEC59 cells than in MMR-proficient HEC59+ch2 cells. Cisplatin was not more potent in generating paclitaxel-resistant variants in the MMR-deficient HEC59 cells. Spontaneous rates of generation of cells resistant to these three drugs were also measured in the HCT116 sublines. MMR-deficient HCT116 cells exhibited rates of generation of resistant variants that were 1.94- and 1.51-fold higher (P <.05) than those in the MMR-proficient cells for topotecan and gemcitabine, respectively; loss of MMR had no effect on the rate of generation of variants resistant to paclitaxel. We conclude that the loss of MMR increases the ability of cisplatin to generate variants resistant to topotecan, gemcitabine, and possibly paclitaxel and that MMR also plays a role in controlling the spontaneous rate of generation of variants resistant to topotecan and gemcitabine.

Antineoplastic Agents↗

PubMed1992

Characterization of form variants of Xenorhabdus luminescens.

From Xenorhabdus luminescens XE-87.3 four variants were isolated. One, which produced a red pigment and antibiotics, was luminescent, and could take up dye from culture media, was considered the primary form (XE-red). A pink-pigmented variant (XE-pink) differed from the primary form only in pigmentation and uptake of dye. Of the two other variants, one produced a yellow pigment and fewer antibiotics (XE-yellow), while the other did not produce a pigment or antibiotics (XE-white). Both were less luminescent, did not take up dye, and had small cell and colony sizes. These two variants were very unstable and shifted to the primary form after 3 to 5 days. It was not possible to separate the primary form and the white variant completely; subcultures of one colony always contained a few colonies of the other variant. The white variant was also found in several other X. luminescens strains. DNA fingerprints showed that all four variants are genetically identical and are therefore derivatives of the same parent. Protein patterns revealed a few differences among the four variants. None of the variants could be considered the secondary form. The pathogenicity of the variants decreased in the following order: XE-red, XE-pink, XE-yellow, and XE-white. The mechanism and function of this variability are discussed.

Animals↗

PubMed2005

Characterization of colony morphology variants isolated from Pseudomonas aeruginosa biofilms.

In this study, we report the isolation of small, rough, strongly cohesive colony morphology variants from aging Pseudomonas aeruginosa PAO1 biofilms. Similar to many of the P. aeruginosa colony morphology variants previously described in the literature, these variants autoaggregate in liquid culture and hyperadhere to solid surfaces. They also exhibit increased hydrophobicity and reduced motility compared to the wild-type parent strain. Despite the similarities in appearance of our colony morphology variant isolates on solid medium, the isolates showed a range of responses in various phenotypic assays. These variants form biofilms with significant three-dimensional structure and more biomass than the wild-type parent. To further explore the nature of the variants, their transcriptional profiles were evaluated. The variants generally showed increased expression of the psl and pel loci, which have been previously implicated in the adherence of P. aeruginosa to solid surfaces. When a mutation in the psl locus was introduced into a colony morphology variant, the colony morphology was only partially affected, but hyperadherence and autoaggregation were lost. Finally, similar colony morphology variants were found in isolates from cystic fibrosis patients. These variants displayed many of the same characteristics as the laboratory variants, suggesting a link between laboratory and cystic fibrosis biofilms.

Bacterial Adhesion↗